rs80086857
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000337.6(SGCD):c.700-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 1,607,908 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000337.6 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0204 AC: 3101AN: 152164Hom.: 90 Cov.: 32
GnomAD3 exomes AF: 0.00499 AC: 1237AN: 248096Hom.: 40 AF XY: 0.00360 AC XY: 485AN XY: 134716
GnomAD4 exome AF: 0.00188 AC: 2741AN: 1455626Hom.: 94 Cov.: 28 AF XY: 0.00158 AC XY: 1145AN XY: 724522
GnomAD4 genome AF: 0.0205 AC: 3116AN: 152282Hom.: 91 Cov.: 32 AF XY: 0.0198 AC XY: 1475AN XY: 74452
ClinVar
Submissions by phenotype
not specified Benign:6
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Variant summary: SGCD c.700-19T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.005 in 248096 control chromosomes, predominantly at a frequency of 0.068 within the African or African-American subpopulation in the gnomAD database, including 39 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2720-fold the estimated maximal pathogenic allele frequency expected for a variant in SGCD causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.700-19T>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating an impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
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Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:2
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not provided Benign:2
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Dilated cardiomyopathy 1L Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at