rs200448085

Variant names:

• chr19-4361740-C-A
• NM_003025.4:c.967G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-4361740-C-A
• chr19-4361740-C-G
• chr19-4361740-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003025.4(SH3GL1):​c.967G>T​(p.Gly323Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G323R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SH3GL1 NM_003025.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3GL1	NM_003025.4	c.967G>T	p.Gly323Trp	missense_variant	Exon 10 of 10	ENST00000269886.7	NP_003016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3GL1	ENST00000269886.7	c.967G>T	p.Gly323Trp	missense_variant	Exon 10 of 10	1	NM_003025.4	ENSP00000269886.2
SH3GL1	ENST00000417295.6	c.823G>T	p.Gly275Trp	missense_variant	Exon 9 of 9	2		ENSP00000404568.2
SH3GL1	ENST00000598564.5	c.775G>T	p.Gly259Trp	missense_variant	Exon 10 of 10	2		ENSP00000470792.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460620 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726724

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-7.5	D;.;D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.77
MutPred		0.62		Loss of disorder (P = 0.0174);.;.;
MVP		0.60
MPC		1.3
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.80
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4361737;