Variant 10-80538374-C-G 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.43C>G(p.Leu15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,411,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

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=0.11804545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2D4B	NM_001388272.1 linkuse as main transcript	c.43C>G	p.Leu15Val	missense_variant	1/8	ENST00000646907.2
SH2D4B	NM_207372.2 linkuse as main transcript	c.43C>G	p.Leu15Val	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2D4B	ENST00000646907.2 linkuse as main transcript	c.43C>G	p.Leu15Val	missense_variant	1/8		NM_001388272.1	P1
SH2D4B	ENST00000339284.6 linkuse as main transcript	c.43C>G	p.Leu15Val	missense_variant	1/7	2			Q5SQS7-2

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000200

AC:

AN:

65052

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

32272

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000701

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.0000977

AC:

123

AN:

1258976

Hom.:

Cov.:

AF XY:

0.0000769

AC XY:

AN XY:

611320

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.000969

Gnomad4 ASJ exome

AF:

0.000381

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000176

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000624

Gnomad4 OTH exome

AF:

0.000312

GnomAD4 genome

AF:

0.000197

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000300

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000476

AC:

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 16, 2022

The c.43C>G (p.L15V) alteration is located in exon 1 (coding exon 1) of the SH2D4B gene. This alteration results from a C to G substitution at nucleotide position 43, causing the leucine (L) at amino acid position 15 to be replaced by a valine (V). 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

-0.42

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0080

D;.

Polyphen

1.0

D;.

Vest4

0.17

MutPred

0.52

Gain of phosphorylation at Y10 (P = 0.2859);Gain of phosphorylation at Y10 (P = 0.2859);

MVP

0.73

MPC

0.27

ClinPred

0.23

GERP RS

5.5

gMVP

0.15

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