chr10-97246305-C-G

Position:

• chr10-97246305-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032900.6(ARHGAP19):​c.960G>C​(p.Leu320Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP19 NM_032900.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.231

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]

ARHGAP19 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP19	NM_032900.6	c.960G>C	p.Leu320Phe	missense_variant	7/12	ENST00000358531.9	NP_116289.4
ARHGAP19	NM_001256423.2	c.933G>C	p.Leu311Phe	missense_variant	7/12		NP_001243352.1
ARHGAP19	NM_001204300.2	c.873G>C	p.Leu291Phe	missense_variant	6/11		NP_001191229.1
ARHGAP19-SLIT1	NR_037909.1	n.1006G>C		non_coding_transcript_exon_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP19	ENST00000358531.9	c.960G>C	p.Leu320Phe	missense_variant	7/12	1	NM_032900.6	ENSP00000351333.4
ARHGAP19-SLIT1	ENST00000479633.2	n.960G>C		non_coding_transcript_exon_variant	7/15	2		ENSP00000473567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.960G>C (p.L320F) alteration is located in exon 7 (coding exon 7) of the ARHGAP19 gene. This alteration results from a G to C substitution at nucleotide position 960, causing the leucine (L) at amino acid position 320 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.
Eigen	Benign	-0.037
Eigen_PC	Benign	-0.063
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;T;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.11	T;D;T
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.45
MutPred		0.63		Loss of stability (P = 0.1246);.;.;
MVP		0.41
MPC		0.59
ClinPred		0.91	D
GERP RS		0.72
Varity_R		0.040
gMVP		0.21

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: chr10-99006062;