Submissions for variant NM_004595.5(SMS):c.410A>G (p.Asp137Gly)

dbSNP: rs1924586809

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn	RCV001171510	SCV001245454	likely pathogenic	Syndromic X-linked intellectual disability Snyder type		criteria provided, single submitter	clinical testing	By means of exome sequencing and subsequent analysis of the genes with the ten highest PEDIA values (PMID 31164752), a possibly disease-causing missense variant in the SMS gene was identified. The sequencing of exon 5 (NM_004595) revealed a hemizygotic base exchange at nucleotide position 410 of the cDNA. The name of the variant is: c.410A> G; p. (Asp137Giy). As a result, the codon for the amino acid aspartic acid (GAT) is replaced by the codon for the amino acid glycine (GGT), it was detected heterozygously in the mother and was not found in the father. In phenotype-related and population-related databases, the above-mentioned missense variant is not listed. The mutation prediction programs MutationTaster, SIFT and PolyPhen-2 estimate the variant as pathogenic, the CADD score is 25.7. It is a highly conserved amino acid that lies in a spermidine synthase domain. The ACMG classification of the variant is: probably pathogenic (PM1 PM2 PP1 PP2 PP3). Certain pathogenic variants in the SMS gene are responsible for Snyder-Robinson syndrome (OMIM # 309583). This syndrome is characterized by moderate intelligence, muscle hypotension, insecure gait, osteoporosis, kyphoscoliosis and facial asymmetry. Inheritance is X-linked recessive.