Genetic Variant SH2D4B:p.Ala220Ser (chr10-80603593-G-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001388272.1(SH2D4B):c.658G>T(p.Ala220Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,560,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A220T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.04

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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27051246).

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.658G>T	p.Ala220Ser	missense	Exon 5 of 8	NP_001375201.1	A0A2R8Y5Q0
SH2D4B	NM_207372.2		c.658G>T	p.Ala220Ser	missense	Exon 5 of 7	NP_997255.2	Q5SQS7-2
SH2D4B	NM_001145719.1		c.511G>T	p.Ala171Ser	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.658G>T	p.Ala220Ser	missense	Exon 5 of 8	ENSP00000494732.1	A0A2R8Y5Q0
SH2D4B	ENST00000339284.6	TSL:2	c.658G>T	p.Ala220Ser	missense	Exon 5 of 7	ENSP00000345295.2	Q5SQS7-2
SH2D4B	ENST00000313455.5	TSL:2	c.511G>T	p.Ala171Ser	missense	Exon 5 of 7	ENSP00000314242.4	Q5SQS7-3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000582

AC:

AN:

171850

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000999

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000497

AC:

AN:

1407828

Hom.:

Cov.:

AF XY:

0.00000432

AC XY:

AN XY:

694650

show subpopulations

African (AFR)

AF:

0.000185

AC:

AN:

32490

American (AMR)

AF:

0.00

AC:

AN:

36728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25246

East Asian (EAS)

AF:

0.00

AC:

AN:

36990

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4772

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083458

Other (OTH)

AF:

0.00

AC:

AN:

58246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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:

0.0000416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0090

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.96

PhyloP100

6.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.1

REVEL

Benign

0.087

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.026

Polyphen

0.67

Vest4

0.38

MutPred

0.24

Gain of phosphorylation at A220 (P = 0.0012)

MVP

0.70

MPC

0.49

ClinPred

0.77

GERP RS

5.1

gMVP

0.12

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over