rs62129346

Variant names:

• chr19-4363292-C-T
• rs62129346
• NM_003025.4:c.728+78G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-4363292-C-T
• chr19-4363292-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003025.4(SH3GL1):​c.728+78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,081,548 control chromosomes in the GnomAD database, including 33,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3662 hom., cov: 34)
  • Exomes 𝑓: 0.25 (29589 hom.)
• Consequence: SH3GL1 NM_003025.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 19-4363292-C-T is Benign according to our data. Variant chr19-4363292-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003025.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL1	NM_003025.4	MANE Select	c.728+78G>A		intron	N/A	NP_003016.1	Q6FGM0
	SH3GL1	NM_001199943.2		c.584+78G>A		intron	N/A	NP_001186872.1	Q99961-2
	SH3GL1	NM_001199944.2		c.536+78G>A		intron	N/A	NP_001186873.1	Q99961-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3GL1	ENST00000269886.7	TSL:1 MANE Select	c.728+78G>A		intron	N/A	ENSP00000269886.2	Q99961-1
	SH3GL1	ENST00000908568.1		c.725+78G>A		intron	N/A	ENSP00000578627.1
	SH3GL1	ENST00000945946.1		c.689+78G>A		intron	N/A	ENSP00000616005.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31649 AN: 152132 Hom.: 3662 Cov.: 34

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.247 AC: 229181 AN: 929298 Hom.: 29589 AF XY: 0.247 AC XY: 117073 AN XY: 473822

African (AFR) AF: 0.0997 AC: 2255 AN: 22624

American (AMR) AF: 0.251 AC: 8633 AN: 34390

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 4808 AN: 21144

East Asian (EAS) AF: 0.107 AC: 3592 AN: 33496

South Asian (SAS) AF: 0.256 AC: 17394 AN: 67904

European-Finnish (FIN) AF: 0.184 AC: 8528 AN: 46254

Middle Eastern (MID) AF: 0.227 AC: 748 AN: 3288

European-Non Finnish (NFE) AF: 0.263 AC: 172735 AN: 657996

Other (OTH) AF: 0.249 AC: 10488 AN: 42202

GnomAD4 genome AF: 0.208 AC: 31657 AN: 152250 Hom.: 3662 Cov.: 34 AF XY: 0.207 AC XY: 15411 AN XY: 74432

African (AFR) AF: 0.105 AC: 4352 AN: 41558

American (AMR) AF: 0.275 AC: 4214 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3470

East Asian (EAS) AF: 0.125 AC: 649 AN: 5178

South Asian (SAS) AF: 0.261 AC: 1261 AN: 4826

European-Finnish (FIN) AF: 0.175 AC: 1853 AN: 10606

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17835 AN: 68000

Other (OTH) AF: 0.231 AC: 486 AN: 2108

Alfa AF: 0.228 Hom.: 534

Bravo AF: 0.208

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.52
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62129346; hg19: chr19-4363289; COSMIC: COSV53656992; COSMIC: COSV53656992;