Variant chr9-129012258-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_020145.4(SH3GLB2):c.602T>G(p.Ile201Ser) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000079 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH3GLB2
NM_020145.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

SH3GLB2 (HGNC:10834): (SH3 domain containing GRB2 like, endophilin B2) Enables identical protein binding activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH3GLB2 links:

SH3GLB2 (HGNC:):

SH3GLB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34666425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GLB2	NM_020145.4 linkuse as main transcript	c.602T>G	p.Ile201Ser	missense_variant	6/11	ENST00000372564.8	NP_064530.1	Q9NR46-1A0A024R896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GLB2	ENST00000372564.8 linkuse as main transcript	c.602T>G	p.Ile201Ser	missense_variant	6/11	1	NM_020145.4	ENSP00000361645.3		Q9NR46-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151714

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000484

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:

0.0000951

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000787

AC:

AN:

1144184

Hom.:

Cov.:

AF XY:

0.0000842

AC XY:

AN XY:

546002

show subpopulations

Gnomad4 AFR exome

AF:

0.0000406

Gnomad4 AMR exome

AF:

0.000326

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000274

Gnomad4 SAS exome

AF:

0.0000372

Gnomad4 FIN exome

AF:

0.000205

Gnomad4 NFE exome

AF:

0.0000676

Gnomad4 OTH exome

AF:

0.0000872

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000329

AC:

AN:

151830

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000951

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

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

Jun 22, 2024

The c.602T>G (p.I201S) alteration is located in exon 6 (coding exon 6) of the SH3GLB2 gene. This alteration results from a T to G substitution at nucleotide position 602, causing the isoleucine (I) at amino acid position 201 to be replaced by a serine (S). 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

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

T;T;.;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

.;D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.91

N;N;N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0070

D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

0.0020

B;B;P;.

Vest4

0.56

MutPred

0.49

Gain of disorder (P = 0.0021);Gain of disorder (P = 0.0021);.;Gain of disorder (P = 0.0021);

MVP

0.56

MPC

0.97

ClinPred

0.86

GERP RS

5.8

Varity_R

0.29

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over