Variant 12-111418702-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005475.3(SH2B3):c.557G>T(p.Ser186Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,486,858 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 48 hom. )

Consequence

SH2B3
NM_005475.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.444

Variant links:

Genes affected

SH2B3 (HGNC:29605): (SH2B adaptor protein 3) This gene encodes a member of the SH2B adaptor family of proteins, which are involved in a range of signaling activities by growth factor and cytokine receptors. The encoded protein is a key negative regulator of cytokine signaling and plays a critical role in hematopoiesis. Mutations in this gene have been associated with susceptibility to celiac disease type 13 and susceptibility to insulin-dependent diabetes mellitus. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

SH2B3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055173934).

BP6

Variant 12-111418702-G-T is Benign according to our data. Variant chr12-111418702-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2672522.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2B3	NM_005475.3 linkuse as main transcript	c.557G>T	p.Ser186Ile	missense_variant	2/8	ENST00000341259.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2B3	ENST00000341259.7 linkuse as main transcript	c.557G>T	p.Ser186Ile	missense_variant	2/8	1	NM_005475.3	P1
SH2B3	ENST00000550925.2 linkuse as main transcript	c.365G>T	p.Ser122Ile	missense_variant	1/2	5

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

773

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0175

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00689

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00575

AC:

522

AN:

90802

Hom.:

AF XY:

0.00634

AC XY:

330

AN XY:

52028

show subpopulations

Gnomad AFR exome

AF:

0.000806

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00521

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.00883

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00658

AC:

8781

AN:

1334840

Hom.:

Cov.:

AF XY:

0.00656

AC XY:

4326

AN XY:

659380

show subpopulations

Gnomad4 AFR exome

AF:

0.000946

Gnomad4 AMR exome

AF:

0.00115

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00425

Gnomad4 FIN exome

AF:

0.0150

Gnomad4 NFE exome

AF:

0.00717

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.00508

AC:

773

AN:

152018

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

432

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0175

Gnomad4 NFE

AF:

0.00689

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00341

Hom.:

Bravo

AF:

0.00358

ESP6500AA

AF:

0.00119

AC:

ESP6500EA

AF:

0.00513

AC:

ExAC

AF:

0.00420

AC:

400

Asia WGS

AF:

0.00322

AC:

AN:

3430

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

SH2B3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.34

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.1

REVEL

Benign

0.011

Sift

Benign

0.069

Sift4G

Benign

0.12

Polyphen

0.080

Vest4

0.13

MVP

0.60

MPC

1.4

ClinPred

0.024

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.34

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