rs961766141

Variant names:

• chr11-73308831-C-A
• rs961766141
• NM_014786.4:c.193C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-73308831-C-A
• chr11-73308831-C-T

Variant summary

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

The NM_014786.4(ARHGEF17):​c.193C>A​(p.Pro65Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000842 in 1,188,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P65S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: ARHGEF17 NM_014786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280
• Publications: 0 publications found

Genes affected

ARHGEF17 (HGNC:21726): (Rho guanine nucleotide exchange factor 17) Enables guanyl-nucleotide exchange factor activity. Acts upstream of or within actin cytoskeleton organization. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF17-AS1 (HGNC:55485): (ARHGEF17 antisense RNA 1)

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=0.18967447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014786.4. 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
	ARHGEF17	NM_014786.4	MANE Select	c.193C>A	p.Pro65Thr	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.531G>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF17	ENST00000263674.4	TSL:1 MANE Select	c.193C>A	p.Pro65Thr	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
	ARHGEF17	ENST00000914587.1		c.193C>A	p.Pro65Thr	missense	Exon 1 of 20	ENSP00000584647.1
	ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.531G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.42e-7 AC: 1 AN: 1188148 Hom.: 0 Cov.: 30 AF XY: 0.00000174 AC XY: 1 AN XY: 573552

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23420

American (AMR) AF: 0.00 AC: 0 AN: 8974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16434

East Asian (EAS) AF: 0.00 AC: 0 AN: 26962

South Asian (SAS) AF: 0.0000211 AC: 1 AN: 47290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 984600

Other (OTH) AF: 0.00 AC: 0 AN: 48820

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.028
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.043
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.020	D
Polyphen		0.60	P
Vest4		0.14
MutPred		0.20		Gain of phosphorylation at P65 (P = 0.044)
MVP		0.31
MPC		0.47
ClinPred		0.25	T
GERP RS		2.6
Varity_R		0.079
gMVP		0.22
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs961766141; hg19: chr11-73019876;