chr4-151133068-AA-CG

Variant names:

• chr4-151133068-AA-CG
• NM_001378122.1:c.2654_2655delTTinsCG
• SH3D19 p.Val885Ala

Variant summary

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

The NM_001378122.1(SH3D19):​c.2654_2655delTTinsCG​(p.Val885Ala) variant causes a missense change. 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: 32)
• Consequence: SH3D19 NM_001378122.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06
• Publications: 0 publications found

Genes affected

SH3D19 (HGNC:30418): (SH3 domain containing 19) This gene encodes a multiple SH3 domain-containing protein, which interacts with other proteins, such as EBP and members of ADAM family, via the SH3 domains. This protein may be involved in suppression of Ras-induced cellular transformation and Ras-mediated activation of ELK1 by EBP, and regulation of ADAM proteins in the signaling of EGFR-ligand shedding. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SH3D19-AS1 (HGNC:58337):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378122.1. 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
	SH3D19	NM_001378122.1	MANE Select	c.2654_2655delTTinsCG	p.Val885Ala	missense	N/A	NP_001365051.1	A0A0U1RQE4
	SH3D19	NM_001378121.1		c.2723_2724delTTinsCG	p.Val908Ala	missense	N/A	NP_001365050.1
	SH3D19	NM_001378123.1		c.2546_2547delTTinsCG	p.Val849Ala	missense	N/A	NP_001365052.1	A0A494C1M0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3D19	ENST00000604030.7	TSL:5 MANE Select	c.2654_2655delTTinsCG	p.Val885Ala	missense	N/A	ENSP00000488951.1	A0A0U1RQE4
	SH3D19	ENST00000409598.8	TSL:1	c.1814_1815delTTinsCG	p.Val605Ala	missense	N/A	ENSP00000387030.4	Q5HYK7-2
	SH3D19	ENST00000427414.2	TSL:1	c.1706_1707delTTinsCG	p.Val569Ala	missense	N/A	ENSP00000415694.1	Q5HYK7-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.1

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: chr4-152054220;