NM_004667.6:c.10969G>A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004667.6(HERC2):c.10969G>A(p.Val3657Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,614,064 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004667.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HERC2 | ENST00000261609.13 | c.10969G>A | p.Val3657Ile | missense_variant | Exon 71 of 93 | 1 | NM_004667.6 | ENSP00000261609.8 | ||
HERC2 | ENST00000650509.1 | n.2680G>A | non_coding_transcript_exon_variant | Exon 19 of 39 | ENSP00000496936.1 |
Frequencies
GnomAD3 genomes AF: 0.00254 AC: 387AN: 152078Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00282 AC: 710AN: 251430Hom.: 3 AF XY: 0.00274 AC XY: 373AN XY: 135886
GnomAD4 exome AF: 0.00346 AC: 5054AN: 1461868Hom.: 11 Cov.: 31 AF XY: 0.00343 AC XY: 2493AN XY: 727244
GnomAD4 genome AF: 0.00254 AC: 387AN: 152196Hom.: 0 Cov.: 31 AF XY: 0.00232 AC XY: 173AN XY: 74412
ClinVar
Submissions by phenotype
not provided Benign:3
HERC2: BP4, BS2 -
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Inborn genetic diseases Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
HERC2-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at