dbSNP rs374274725: SH3GLB2:p.Gly283Cys (chr9-129009339-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_020145.4(SH3GLB2):c.847G>T(p.Gly283Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,394,956 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. G283S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SH3GLB2
NM_020145.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.33

Publications

0 publications found

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:

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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=0.2631899).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020145.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3GLB2	NM_020145.4	MANE Select	c.847G>T	p.Gly283Cys	missense	Exon 10 of 11	NP_064530.1	Q9NR46-1
SH3GLB2	NM_001438434.1		c.919G>T	p.Gly307Cys	missense	Exon 10 of 11	NP_001425363.1
SH3GLB2	NM_001369913.1		c.907G>T	p.Gly303Cys	missense	Exon 12 of 13	NP_001356842.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3GLB2	ENST00000372564.8	TSL:1 MANE Select	c.847G>T	p.Gly283Cys	missense	Exon 10 of 11	ENSP00000361645.3	Q9NR46-1
SH3GLB2	ENST00000372554.8	TSL:1	c.874G>T	p.Gly292Cys	missense	Exon 12 of 13	ENSP00000361634.4	Q9NR46-2
SH3GLB2	ENST00000372559.5	TSL:1	c.847G>T	p.Gly283Cys	missense	Exon 10 of 12	ENSP00000361640.1	Q9NR46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1394956

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31548

American (AMR)

AF:

0.00

AC:

AN:

35450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24770

East Asian (EAS)

AF:

0.00

AC:

AN:

35746

South Asian (SAS)

AF:

0.00

AC:

AN:

78936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076112

Other (OTH)

AF:

0.00

AC:

AN:

57762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

0.15

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.015

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

2.3

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.11

Sift

Uncertain

0.026

Sift4G

Uncertain

0.028

Polyphen

0.88

Vest4

0.23

MutPred

0.46

Gain of catalytic residue at P282 (P = 0.0118)

MVP

0.48

MPC

0.31

ClinPred

0.91

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.37

Mutation Taster

=83/17

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