Genetic Variant SH3BGR:c.-96C>G (chr21-39452001-C-G) – 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_007341.3(SH3BGR):c.-96C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SH3BGR
NM_007341.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

0 publications found

Variant links:

Genes affected

SH3BGR (HGNC:10822): (SH3 domain binding glutamate rich protein) Predicted to enable SH3 domain binding activity. Predicted to be involved in protein-containing complex assembly. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

SH3BGR links:

GET1-SH3BGR (HGNC:54635): (GET1-SH3BGR readthrough) This locus represents naturally occurring readthrough transcription between the neighboring WRB (tryptophan rich basic protein) and SH3BGR (SH3 domain binding glutamate-rich protein) genes on chromosome 21. Readthrough transcripts may encode fusion proteins that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

GET1-SH3BGR 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=0.09337801).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGR	NM_007341.3 link	c.-96C>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000333634.10	NP_031367.2	P55822

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BGR	ENST00000333634.10 link	c.-96C>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_007341.3	ENSP00000332513.5		A0A804CBI3
GET1-SH3BGR	ENST00000647779.1 link	c.337-10374C>G		intron_variant	Intron 3 of 8			ENSP00000497977.1		A0A3B3ITX9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 19, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.94C>G (p.L32V) alteration is located in exon 1 (coding exon 1) of the SH3BGR gene. This alteration results from a C to G substitution at nucleotide position 94, causing the leucine (L) at amino acid position 32 to be replaced by a valine (V). 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

Benign

0.071

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.43

M_CAP

Benign

0.0078

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.18

REVEL

Benign

0.073

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.024

Vest4

0.25

MutPred

0.22

Gain of catalytic residue at L32 (P = 0.0961);

MVP

0.014

MPC

0.19

ClinPred

0.36

GERP RS

1.7

PromoterAI

0.082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.16

gMVP

0.10

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over