Variant 9-17789536-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003026.5(SH3GL2):c.610C>T(p.Leu204Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,264 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SH3GL2
NM_003026.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.36

Variant links:

Genes affected

SH3GL2 (HGNC:10831): (SH3 domain containing GRB2 like 2, endophilin A1) Enables identical protein binding activity. Involved in negative regulation of blood-brain barrier permeability; negative regulation of gene expression; and negative regulation of protein phosphorylation. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH3GL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27725217).

BS2

High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SH3GL2	NM_003026.5 linkuse as main transcript	c.610C>T	p.Leu204Phe	missense_variant	6/9	ENST00000380607.5	NP_003017.1
SH3GL2	XM_011518005.4 linkuse as main transcript	c.712C>T	p.Leu238Phe	missense_variant	6/9		XP_011516307.1
SH3GL2	XM_047423730.1 linkuse as main transcript	c.505C>T	p.Leu169Phe	missense_variant	6/9		XP_047279686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GL2	ENST00000380607.5 linkuse as main transcript	c.610C>T	p.Leu204Phe	missense_variant	6/9	1	NM_003026.5	ENSP00000369981	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250622

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135428

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:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461134

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726898

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:

0.0000279

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

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

Jan 08, 2024

The c.610C>T (p.L204F) alteration is located in exon 6 (coding exon 6) of the SH3GL2 gene. This alteration results from a C to T substitution at nucleotide position 610, causing the leucine (L) at amino acid position 204 to be replaced by a phenylalanine (F). 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

0.53

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.026

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.33

Sift

Benign

0.32

Sift4G

Benign

0.31

Polyphen

0.36

Vest4

0.34

MVP

0.53

MPC

1.2

ClinPred

0.43

GERP RS

6.0

Varity_R

0.54

gMVP

0.57

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