dbSNP rs770519509: SH2D4B:p.Arg227Ser (chr10-80603614-C-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.679C>A(p.Arg227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R227C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.43

Publications

0 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:

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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=0.06846893).

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.679C>A	p.Arg227Ser	missense	Exon 5 of 8	NP_001375201.1	A0A2R8Y5Q0
SH2D4B	NM_207372.2		c.679C>A	p.Arg227Ser	missense	Exon 5 of 7	NP_997255.2	Q5SQS7-2
SH2D4B	NM_001145719.1		c.532C>A	p.Arg178Ser	missense	Exon 5 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.679C>A	p.Arg227Ser	missense	Exon 5 of 8	ENSP00000494732.1	A0A2R8Y5Q0
SH2D4B	ENST00000339284.6	TSL:2	c.679C>A	p.Arg227Ser	missense	Exon 5 of 7	ENSP00000345295.2	Q5SQS7-2
SH2D4B	ENST00000313455.5	TSL:2	c.532C>A	p.Arg178Ser	missense	Exon 5 of 7	ENSP00000314242.4	Q5SQS7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424776

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32926

American (AMR)

AF:

0.00

AC:

AN:

38636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25430

East Asian (EAS)

AF:

0.00

AC:

AN:

37956

South Asian (SAS)

AF:

0.00

AC:

AN:

81520

European-Finnish (FIN)

AF:

0.0000198

AC:

AN:

50560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4990

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093770

Other (OTH)

AF:

0.00

AC:

AN:

58988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.84

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.76

M_CAP

Benign

0.0044

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.89

PhyloP100

1.4

PrimateAI

Benign

0.37

PROVEAN

Benign

1.2

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.79

Vest4

0.37

MutPred

0.29

Gain of phosphorylation at R227 (P = 0.0016)

MVP

0.41

MPC

0.17

ClinPred

0.46

GERP RS

5.1

gMVP

0.11

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over