3-138372905-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001085049.3(MRAS):āc.22A>Gā(p.Ser8Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000229 in 1,546,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001085049.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000539 AC: 104AN: 192782Hom.: 0 AF XY: 0.000670 AC XY: 71AN XY: 105960
GnomAD4 exome AF: 0.000235 AC: 328AN: 1394592Hom.: 1 Cov.: 33 AF XY: 0.000316 AC XY: 219AN XY: 692462
GnomAD4 genome AF: 0.000171 AC: 26AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74482
ClinVar
Submissions by phenotype
not provided Benign:2
Variant summary: The MRAS c.22A>G (p.Ser8Gly) variant involves the alteration of a conserved nucleotide. 2/3 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 88/120948 control chromosomes from ExAC, predominantly observed in the South Asian subpopulation at a frequency of 0.005263 (86/16342). This frequency is about 2105 times the estimated maximal expected allele frequency of a pathogenic MRAS variant (0.0000025), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as likely benign. -
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Inborn genetic diseases Uncertain:1
The p.S8G variant (also known as c.22A>G), located in coding exon 1 of the MRAS gene, results from an A to G substitution at nucleotide position 22. The serine at codon 8 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at