1-16206328-G-C

Position:

• chr1-16206328-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000270747.8(ARHGEF19):​c.1150C>G​(p.Leu384Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ARHGEF19 ENST00000270747.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

Genes affected

ARHGEF19 (HGNC:26604): (Rho guanine nucleotide exchange factor 19) Guanine nucleotide exchange factors (GEFs) such as ARHGEF19 accelerate the GTPase activity of Rho GTPases (see RHOA, MIM 165390).[supplied by OMIM, Dec 2008]

ARHGEF19 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42117786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF19	NM_153213.5	c.1150C>G	p.Leu384Val	missense_variant	7/16	ENST00000270747.8	NP_694945.2
ARHGEF19	XM_011540706.4	c.1150C>G	p.Leu384Val	missense_variant	8/17		XP_011539008.1
ARHGEF19	XR_946544.2	n.1330C>G		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF19	ENST00000270747.8	c.1150C>G	p.Leu384Val	missense_variant	7/16	1	NM_153213.5	ENSP00000270747.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

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

Feb 26, 2024

The c.1150C>G (p.L384V) alteration is located in exon 7 (coding exon 6) of the ARHGEF19 gene. This alteration results from a C to G substitution at nucleotide position 1150, causing the leucine (L) at amino acid position 384 to be replaced by a valine (V). 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	Uncertain	0.36
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;.
Eigen	Benign	-0.047
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	0.96	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.21
Sift	Benign	0.31	T;T
Sift4G	Benign	0.16	T;D
Polyphen		0.50	P;.
Vest4		0.43
MutPred		0.65		Loss of stability (P = 0.1775);.;
MVP		0.72
MPC		0.89
ClinPred		0.97	D
GERP RS		3.0
Varity_R		0.53
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-16532823;