Variant 15-83568655-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_003027.5(SH3GL3):c.314G>A(p.Gly105Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SH3GL3
NM_003027.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

Variant links:

Genes affected

SH3GL3 (HGNC:10832): (SH3 domain containing GRB2 like 3, endophilin A3) Enables identical protein binding activity. Predicted to be involved in synaptic vesicle uncoating. Predicted to be located in acrosomal vesicle; early endosome membrane; and presynapse. Predicted to be part of early endosome. Predicted to be active in glutamatergic synapse; postsynaptic density, intracellular component; and postsynaptic endosome. [provided by Alliance of Genome Resources, Apr 2022]

SH3GL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3GL3	NM_003027.5 linkuse as main transcript	c.314G>A	p.Gly105Glu	missense_variant	4/9	ENST00000427482.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3GL3	ENST00000427482.7 linkuse as main transcript	c.314G>A	p.Gly105Glu	missense_variant	4/9	1	NM_003027.5	P1	Q99963-1
SH3GL3	ENST00000563901.5 linkuse as main transcript	c.*109G>A		3_prime_UTR_variant, NMD_transcript_variant	4/9	1
SH3GL3	ENST00000324537.5 linkuse as main transcript	c.338G>A	p.Gly113Glu	missense_variant	7/12	2			Q99963-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251066

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Dec 21, 2023

The c.314G>A (p.G105E) alteration is located in exon 4 (coding exon 4) of the SH3GL3 gene. This alteration results from a G to A substitution at nucleotide position 314, causing the glycine (G) at amino acid position 105 to be replaced by a glutamic acid (E). 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

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.090

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.31

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Uncertain

0.033

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-7.1

D;D

REVEL

Uncertain

0.59

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

D;D

Vest4

0.78

MutPred

0.69

Gain of disorder (P = 0.1112);.;

MVP

0.89

MPC

1.4

ClinPred

1.0

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.93

gMVP

0.67

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