Variant chr15-83568651-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003027.5(SH3GL3):c.310C>G(p.Leu104Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SH3GL3
NM_003027.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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:

SH3GL3 (HGNC:):

SH3GL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL3	NM_003027.5 linkuse as main transcript	c.310C>G	p.Leu104Val	missense_variant	4/9	ENST00000427482.7	NP_003018.3	Q99963-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SH3GL3	ENST00000427482.7 linkuse as main transcript	c.310C>G	p.Leu104Val	missense_variant	4/9	1	NM_003027.5	ENSP00000391372.2	Q99963-1
SH3GL3	ENST00000563901.5 linkuse as main transcript	n.*105C>G		non_coding_transcript_exon_variant	4/9	1		ENSP00000456249.1	H3BRH8
SH3GL3	ENST00000563901.5 linkuse as main transcript	n.*105C>G		3_prime_UTR_variant	4/9	1		ENSP00000456249.1	H3BRH8
SH3GL3	ENST00000324537.5 linkuse as main transcript	c.334C>G	p.Leu112Val	missense_variant	7/12	2		ENSP00000320092.5	Q99963-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461470

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727050

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 31, 2024

The c.310C>G (p.L104V) alteration is located in exon 4 (coding exon 4) of the SH3GL3 gene. This alteration results from a C to G substitution at nucleotide position 310, causing the leucine (L) at amino acid position 104 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

0.20

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.75

P;P

Vest4

0.67

MutPred

0.72

Gain of methylation at K99 (P = 0.0805);.;

MVP

0.61

MPC

1.3

ClinPred

0.96

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.89

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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