Genetic Variant NM_001388272.1:c.220G>A (chr10-80570189-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001388272.1(SH2D4B):c.220G>A(p.Ala74Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11704618).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388272.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH2D4B	NM_001388272.1	MANE Select	c.220G>A	p.Ala74Thr	missense	Exon 2 of 8	NP_001375201.1	A0A2R8Y5Q0
SH2D4B	NM_207372.2		c.220G>A	p.Ala74Thr	missense	Exon 2 of 7	NP_997255.2	Q5SQS7-2
SH2D4B	NM_001145719.1		c.73G>A	p.Ala25Thr	missense	Exon 2 of 7	NP_001139191.1	Q5SQS7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH2D4B	ENST00000646907.2	MANE Select	c.220G>A	p.Ala74Thr	missense	Exon 2 of 8	ENSP00000494732.1	A0A2R8Y5Q0
SH2D4B	ENST00000339284.6	TSL:2	c.220G>A	p.Ala74Thr	missense	Exon 2 of 7	ENSP00000345295.2	Q5SQS7-2
SH2D4B	ENST00000313455.5	TSL:2	c.73G>A	p.Ala25Thr	missense	Exon 2 of 7	ENSP00000314242.4	Q5SQS7-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.86

M_CAP

Benign

0.0025

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

2.6

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

REVEL

Benign

0.070

Sift

Benign

0.14

Sift4G

Benign

0.52

Polyphen

0.0040

Vest4

0.19

MutPred

0.46

Loss of stability (P = 0.0359)

MVP

0.29

MPC

0.15

ClinPred

0.31

GERP RS

4.7

gMVP

0.068

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over