10-97235255-T-C

Variant names:

• chr10-97235255-T-C
• NM_032900.6:c.1246A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032900.6(ARHGAP19):​c.1246A>G​(p.Lys416Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ARHGAP19 NM_032900.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24601859).

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.1246A>G	p.Lys416Glu	missense	Exon 9 of 12	NP_116289.4
	ARHGAP19	NM_001256423.2		c.1219A>G	p.Lys407Glu	missense	Exon 9 of 12	NP_001243352.1	Q14CB8-3
	ARHGAP19	NM_001204300.2		c.1159A>G	p.Lys387Glu	missense	Exon 8 of 11	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.1246A>G	p.Lys416Glu	missense	Exon 9 of 12	ENSP00000351333.4	Q14CB8-1
	ARHGAP19	ENST00000358308.7	TSL:1	c.1159A>G	p.Lys387Glu	missense	Exon 8 of 11	ENSP00000351058.4	Q14CB8-6
	ARHGAP19-SLIT1	ENST00000479633.2	TSL:2	n.1246A>G		non_coding_transcript_exon	Exon 9 of 15	ENSP00000473567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461706 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.014	D
Polyphen		0.95	P
Vest4		0.29
MutPred		0.25		Loss of methylation at K416 (P = 0.0068)
MVP		0.29
MPC		0.58
ClinPred		0.95	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.23
gMVP		0.29
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr10-98995012;