8-19393380-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_022071.4(SH2D4A):c.1111C>A(p.Leu371Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000396 in 1,614,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00041 ( 1 hom. )
Consequence
SH2D4A
NM_022071.4 missense
NM_022071.4 missense
Scores
4
9
5
Clinical Significance
Conservation
PhyloP100: 3.86
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2D4A | NM_022071.4 | c.1111C>A | p.Leu371Ile | missense_variant | 9/10 | ENST00000265807.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2D4A | ENST00000265807.8 | c.1111C>A | p.Leu371Ile | missense_variant | 9/10 | 2 | NM_022071.4 | P1 | |
SH2D4A | ENST00000519207.5 | c.1111C>A | p.Leu371Ile | missense_variant | 9/10 | 1 | P1 | ||
SH2D4A | ENST00000518040.5 | c.976C>A | p.Leu326Ile | missense_variant | 8/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000127 AC: 32AN: 251430Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135886
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GnomAD4 exome AF: 0.000415 AC: 606AN: 1461876Hom.: 1 Cov.: 31 AF XY: 0.000404 AC XY: 294AN XY: 727240
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74502
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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 | Jan 26, 2022 | The c.1111C>A (p.L371I) alteration is located in exon 9 (coding exon 8) of the SH2D4A gene. This alteration results from a C to A substitution at nucleotide position 1111, causing the leucine (L) at amino acid position 371 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;.;H
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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