19-4361738-CCC-TCG

Variant names:

• chr19-4361738-CCC-TCG
• NM_003025.4:c.967_969delGGGinsCGA
• SH3GL1 p.Gly323Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003025.4(SH3GL1):​c.967_969delGGGinsCGA​(p.Gly323Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3GL1 NM_003025.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.72
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.967_969delGGGinsCGA	p.Gly323Arg	missense	N/A	NP_003016.1	Q6FGM0
	SH3GL1	NM_001199943.2		c.823_825delGGGinsCGA	p.Gly275Arg	missense	N/A	NP_001186872.1	Q99961-2
	SH3GL1	NM_001199944.2		c.775_777delGGGinsCGA	p.Gly259Arg	missense	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.967_969delGGGinsCGA	p.Gly323Arg	missense	N/A	ENSP00000269886.2	Q99961-1
	SH3GL1	ENST00000908568.1		c.964_966delGGGinsCGA	p.Gly322Arg	missense	N/A	ENSP00000578627.1
	SH3GL1	ENST00000945946.1		c.928_930delGGGinsCGA	p.Gly310Arg	missense	N/A	ENSP00000616005.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-4361735;