chr12-7690390-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM5BP4_StrongBP6_Very_StrongBS2
The NM_020634.3(GDF3):c.583C>T(p.Arg195Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,613,998 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. R195Q) has been classified as Pathogenic.
Frequency
Consequence
NM_020634.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF3 | NM_020634.3 | c.583C>T | p.Arg195Trp | missense_variant | 2/2 | ENST00000329913.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF3 | ENST00000329913.4 | c.583C>T | p.Arg195Trp | missense_variant | 2/2 | 1 | NM_020634.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00153 AC: 233AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000465 AC: 117AN: 251478Hom.: 0 AF XY: 0.000375 AC XY: 51AN XY: 135914
GnomAD4 exome AF: 0.000215 AC: 315AN: 1461820Hom.: 1 Cov.: 34 AF XY: 0.000223 AC XY: 162AN XY: 727236
GnomAD4 genome AF: 0.00158 AC: 240AN: 152178Hom.: 1 Cov.: 32 AF XY: 0.00167 AC XY: 124AN XY: 74404
ClinVar
Submissions by phenotype
GDF3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 03, 2019 | 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). - |
Klippel-Feil syndrome 3, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 09, 2022 | - - |
Klippel-Feil syndrome 3, autosomal dominant;C3150968:Microphthalmia, isolated, with coloboma 6;C3150969:Isolated microphthalmia 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 28, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at