Variant chr19-4361642-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003025.4(SH3GL1):c.1065C>T(p.Phe355Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,609,498 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 72 hom. )

Consequence

SH3GL1
NM_003025.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.21

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 19-4361642-G-A is Benign according to our data. Variant chr19-4361642-G-A is described in ClinVar as [Benign]. Clinvar id is 773078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.21 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1773/152294) while in subpopulation AFR AF= 0.022 (914/41544). AF 95% confidence interval is 0.0208. There are 13 homozygotes in gnomad4. There are 818 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1773 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL1	NM_003025.4 linkuse as main transcript	c.1065C>T	p.Phe355Phe	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.1065C>T	p.Phe355Phe	synonymous_variant	10/10	1	NM_003025.4	ENSP00000269886.2	Q99961-1
SH3GL1	ENST00000417295.6 linkuse as main transcript	c.921C>T	p.Phe307Phe	synonymous_variant	9/9	2		ENSP00000404568.2	Q99961-2
SH3GL1	ENST00000598564.5 linkuse as main transcript	c.873C>T	p.Phe291Phe	synonymous_variant	10/10	2		ENSP00000470792.1	Q99961-3

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1776

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.00776

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00750

AC:

1853

AN:

247020

Hom.:

AF XY:

0.00767

AC XY:

1028

AN XY:

134028

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.00565

Gnomad ASJ exome

AF:

0.00879

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00745

Gnomad FIN exome

AF:

0.00209

Gnomad NFE exome

AF:

0.00778

Gnomad OTH exome

AF:

0.00923

GnomAD4 exome

AF:

0.00753

AC:

10980

AN:

1457204

Hom.:

Cov.:

AF XY:

0.00769

AC XY:

5579

AN XY:

725080

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.00900

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00747

Gnomad4 FIN exome

AF:

0.00249

Gnomad4 NFE exome

AF:

0.00732

Gnomad4 OTH exome

AF:

0.0103

GnomAD4 genome

AF:

0.0116

AC:

1773

AN:

152294

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

818

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0220

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00981

EpiControl

AF:

0.00872

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 19, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.5

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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