Variant 19-4362694-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003025.4(SH3GL1):c.771C>G(p.Pro257Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,613,810 control chromosomes in the GnomAD database, including 73,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8248 hom., cov: 34)

Exomes 𝑓: 0.29 ( 65746 hom. )

Consequence

SH3GL1
NM_003025.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.285

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=-0.69).

BP6

Variant 19-4362694-G-C is Benign according to our data. Variant chr19-4362694-G-C is described in ClinVar as [Benign]. Clinvar id is 1238058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.285 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GL1	NM_003025.4 linkuse as main transcript	c.771C>G	p.Pro257Pro	synonymous_variant	8/10	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.771C>G	p.Pro257Pro	synonymous_variant	8/10	1	NM_003025.4	ENSP00000269886.2	Q99961-1
SH3GL1	ENST00000417295.6 linkuse as main transcript	c.627C>G	p.Pro209Pro	synonymous_variant	7/9	2		ENSP00000404568.2	Q99961-2
SH3GL1	ENST00000598564.5 linkuse as main transcript	c.579C>G	p.Pro193Pro	synonymous_variant	8/10	2		ENSP00000470792.1	Q99961-3

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48683

AN:

152116

Hom.:

8240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.339

AC:

85075

AN:

251202

Hom.:

15638

AF XY:

0.331

AC XY:

45015

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.461

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.583

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.326

Gnomad NFE exome

AF:

0.272

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.292

AC:

427156

AN:

1461576

Hom.:

65746

Cov.:

AF XY:

0.292

AC XY:

212481

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.337

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.584

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.331

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.320

AC:

48714

AN:

152234

Hom.:

8248

Cov.:

AF XY:

0.325

AC XY:

24177

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.305

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.331

Gnomad4 NFE

AF:

0.271

Gnomad4 OTH

AF:

0.333

Alfa

AF:

0.159

Hom.:

286

Bravo

AF:

0.328

Asia WGS

AF:

0.428

AC:

1485

AN:

3478

EpiCase

AF:

0.283

EpiControl

AF:

0.274

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Acute myeloid leukemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.0

DANN

Benign

0.75

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