Variant 10-80603649-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388272.1(SH2D4B):c.714C>A(p.His238Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.702

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12611315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SH2D4B	NM_001388272.1 linkuse as main transcript	c.714C>A	p.His238Gln	missense_variant	5/8	ENST00000646907.2	NP_001375201.1
SH2D4B	NM_207372.2 linkuse as main transcript	c.714C>A	p.His238Gln	missense_variant	5/7		NP_997255.2
SH2D4B	NM_001145719.1 linkuse as main transcript	c.567C>A	p.His189Gln	missense_variant	5/7		NP_001139191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2D4B	ENST00000646907.2 linkuse as main transcript	c.714C>A	p.His238Gln	missense_variant	5/8		NM_001388272.1	ENSP00000494732	P1
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.714C>A	p.His238Gln	missense_variant	5/7	2		ENSP00000345295		Q5SQS7-2
SH2D4B	ENST00000313455.5 linkuse as main transcript	c.567C>A	p.His189Gln	missense_variant	5/7	2		ENSP00000314242		Q5SQS7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230298

Hom.:

AF XY:

0.00

AC XY:

AN XY:

124716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000590

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

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

Feb 05, 2024

The c.714C>A (p.H238Q) alteration is located in exon 5 (coding exon 5) of the SH2D4B gene. This alteration results from a C to A substitution at nucleotide position 714, causing the histidine (H) at amino acid position 238 to be replaced by a glutamine (Q). 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

-0.39

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.50

T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.89

N;.;N

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;.;D

Sift4G

Uncertain

0.011

D;.;D

Polyphen

0.0010

B;.;B

Vest4

0.21

MutPred

0.35

Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);.;

MVP

0.27

MPC

0.15

ClinPred

0.60

GERP RS

1.9

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over