Variant 10-80538367-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001388272.1(SH2D4B):c.36C>A(p.Asp12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.660

Variant links:

Genes affected

SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH2D4B links:

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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	Protein	UniProt
SH2D4B	NM_001388272.1 link	c.36C>A	p.Asp12Glu	missense_variant	1/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2 link	c.36C>A	p.Asp12Glu	missense_variant	1/7		NP_997255.2	Q5SQS7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2 link	c.36C>A	p.Asp12Glu	missense_variant	1/8		NM_001388272.1	ENSP00000494732.1		A0A2R8Y5Q0
SH2D4B	ENST00000339284.6 link	c.36C>A	p.Asp12Glu	missense_variant	1/7	2		ENSP00000345295.2		Q5SQS7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1251268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

606790

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 04, 2024

The c.36C>A (p.D12E) alteration is located in exon 1 (coding exon 1) of the SH2D4B gene. This alteration results from a C to A substitution at nucleotide position 36, causing the aspartic acid (D) at amino acid position 12 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.0098

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.23

Sift

Benign

0.083

T;.

Sift4G

Benign

0.10

T;.

Polyphen

1.0

D;.

Vest4

0.35

MutPred

0.61

Loss of phosphorylation at Y10 (P = 0.1774);Loss of phosphorylation at Y10 (P = 0.1774);

MVP

0.58

MPC

0.54

ClinPred

0.98

GERP RS

3.7

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over