9-127742953-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_170600.3(SH2D3C):c.1812A>G(p.Ile604Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000174 in 1,613,380 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
SH2D3C
NM_170600.3 missense
NM_170600.3 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 0.993
Genes affected
SH2D3C (HGNC:16884): (SH2 domain containing 3C) This gene encodes an adaptor protein and member of a cytoplasmic protein family involved in cell migration. The encoded protein contains a putative Src homology 2 (SH2) domain and guanine nucleotide exchange factor-like domain which allows this signaling protein to form a complex with scaffolding protein Crk-associated substrate. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2D3C | NM_170600.3 | c.1812A>G | p.Ile604Met | missense_variant | 8/12 | ENST00000314830.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2D3C | ENST00000314830.13 | c.1812A>G | p.Ile604Met | missense_variant | 8/12 | 1 | NM_170600.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152218Hom.: 0 Cov.: 33
GnomAD3 genomes
?
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33
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GnomAD3 exomes AF: 0.000156 AC: 39AN: 250188Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135432
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GnomAD4 exome AF: 0.000173 AC: 253AN: 1461044Hom.: 0 Cov.: 30 AF XY: 0.000172 AC XY: 125AN XY: 726874
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74488
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2022 | The c.1812A>G (p.I604M) alteration is located in exon 8 (coding exon 8) of the SH2D3C gene. This alteration results from a A to G substitution at nucleotide position 1812, causing the isoleucine (I) at amino acid position 604 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
P;D;.;.;D;.
Vest4
MVP
MPC
1.2
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at