1-1232666-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PM1PM2BP4_StrongBP6_Very_Strong
The NM_080605.4(B3GALT6):c.388G>A(p.Glu130Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,335,734 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E130G) has been classified as Uncertain significance.
Frequency
Consequence
NM_080605.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000193 AC: 29AN: 150586Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000296 AC: 34AN: 114862Hom.: 0 AF XY: 0.000282 AC XY: 19AN XY: 67328
GnomAD4 exome AF: 0.000154 AC: 182AN: 1185148Hom.: 1 Cov.: 30 AF XY: 0.000153 AC XY: 88AN XY: 576560
GnomAD4 genome AF: 0.000193 AC: 29AN: 150586Hom.: 0 Cov.: 33 AF XY: 0.000177 AC XY: 13AN XY: 73504
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: B3GALT6 c.388G>A (p.Glu130Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 1335734 control chromosomes, predominantly at a frequency of 0.0064 within the Ashkenazi Jewish subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 6-fold of the estimated maximal expected allele frequency for a pathogenic variant in B3GALT6 causing Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures phenotype (0.0011). To our knowledge, no occurrence of c.388G>A in individuals affected with Spondyloepimetaphyseal dysplasia or other B3GALT6-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 582960). Based on the evidence outlined above, the variant was classified as likely benign. -
not provided Benign:1
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Spondyloepimetaphyseal dysplasia with joint laxity;C3809210:Ehlers-Danlos syndrome, spondylodysplastic type, 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at