chr10-97244013-AAC-GAT

Variant names:

• chr10-97244013-AAC-GAT
• NM_032900.6:c.1138_1140delGTTinsATC
• ARHGAP19 p.Val380Ile

Variant summary

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

The NM_032900.6(ARHGAP19):​c.1138_1140delGTTinsATC​(p.Val380Ile) 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: 31)
• Consequence: ARHGAP19 NM_032900.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.04
• Publications: 0 publications found

Genes affected

ARHGAP19 (HGNC:23724): (Rho GTPase activating protein 19) Members of the ARHGAP family, such as ARHGAP19, encode negative regulators of Rho GTPases (see RHOA; MIM 165390), which are involved in cell migration, proliferation, and differentiation, actin remodeling, and G1 cell cycle progression (Lv et al., 2007 [PubMed 17454002]).[supplied by OMIM, Mar 2008]

ARHGAP19-SLIT1 (HGNC:48348): (ARHGAP19-SLIT1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring Rho GTPase activating protein 19 (ARHGAP19) and slit homolog 1 (SLIT1) genes on chromosome 10. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032900.6. 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
	ARHGAP19	NM_032900.6	MANE Select	c.1138_1140delGTTinsATC	p.Val380Ile	missense	N/A	NP_116289.4
	ARHGAP19	NM_001256423.2		c.1111_1113delGTTinsATC	p.Val371Ile	missense	N/A	NP_001243352.1	Q14CB8-3
	ARHGAP19	NM_001204300.2		c.1051_1053delGTTinsATC	p.Val351Ile	missense	N/A	NP_001191229.1	Q14CB8-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP19	ENST00000358531.9	TSL:1 MANE Select	c.1138_1140delGTTinsATC	p.Val380Ile	missense	N/A	ENSP00000351333.4	Q14CB8-1
	ARHGAP19	ENST00000358308.7	TSL:1	c.1051_1053delGTTinsATC	p.Val351Ile	missense	N/A	ENSP00000351058.4	Q14CB8-6
	ARHGAP19-SLIT1	ENST00000479633.2	TSL:2	n.1138_1140delGTTinsATC		non_coding_transcript_exon	Exon 8 of 15	ENSP00000473567.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0

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: chr10-99003770;