Variant 19-4361606-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003025.4(SH3GL1):c.1101G>A(p.Pro367Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,595,932 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 41 hom. )

Consequence

SH3GL1
NM_003025.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.83

Variant links:

Genes affected

SH3GL1 (HGNC:10830): (SH3 domain containing GRB2 like 1, endophilin A2) This gene encodes a member of the endophilin family of Src homology 3 domain-containing proteins. The encoded protein is involved in endocytosis and may also play a role in the cell cycle. Overexpression of this gene may play a role in leukemogenesis, and the encoded protein has been implicated in acute myeloid leukemia as a fusion partner of the myeloid-lymphoid leukemia protein. Pseudogenes of this gene are located on the long arm of chromosomes 11 and 17. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

SH3GL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 19-4361606-C-T is Benign according to our data. Variant chr19-4361606-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3067189.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.83 with no splicing effect.

BS2

High AC in GnomAd4 at 676 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL1	NM_003025.4 linkuse as main transcript	c.1101G>A	p.Pro367Pro	synonymous_variant	10/10	ENST00000269886.7	NP_003016.1	Q99961-1Q6FGM0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SH3GL1	ENST00000269886.7 linkuse as main transcript	c.1101G>A	p.Pro367Pro	synonymous_variant	10/10	1	NM_003025.4	ENSP00000269886.2	Q99961-1
SH3GL1	ENST00000417295.6 linkuse as main transcript	c.957G>A	p.Pro319Pro	synonymous_variant	9/9	2		ENSP00000404568.2	Q99961-2
SH3GL1	ENST00000598564.5 linkuse as main transcript	c.909G>A	p.Pro303Pro	synonymous_variant	10/10	2		ENSP00000470792.1	Q99961-3

Frequencies

GnomAD3 genomes

AF:

0.00444

AC:

676

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00744

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00390

AC:

922

AN:

236624

Hom.:

AF XY:

0.00395

AC XY:

510

AN XY:

128984

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.00167

Gnomad ASJ exome

AF:

0.000836

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00123

Gnomad FIN exome

AF:

0.00465

Gnomad NFE exome

AF:

0.00647

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00644

AC:

9296

AN:

1443706

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

4474

AN XY:

717902

show subpopulations

Gnomad4 AFR exome

AF:

0.000960

Gnomad4 AMR exome

AF:

0.00198

Gnomad4 ASJ exome

AF:

0.000739

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000921

Gnomad4 FIN exome

AF:

0.00490

Gnomad4 NFE exome

AF:

0.00770

Gnomad4 OTH exome

AF:

0.00572

GnomAD4 genome

AF:

0.00444

AC:

676

AN:

152226

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00622

Gnomad4 NFE

AF:

0.00744

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00310

Hom.:

Bravo

AF:

0.00421

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 11, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

SH3GL1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

1.0

DANN

Benign

0.93

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