NM_014786.4:c.232C>G

Variant names:

• chr11-73308870-C-G
• rs944923296
• NM_014786.4:c.232C>G

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.232C>G​(p.Leu78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,204,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. L78F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: ARHGEF17 NM_014786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.805
• 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=0.20768416).

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.232C>G	p.Leu78Val	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.492G>C		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.232C>G	p.Leu78Val	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
	ARHGEF17	ENST00000914587.1		c.232C>G	p.Leu78Val	missense	Exon 1 of 20	ENSP00000584647.1
	ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.492G>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1204496 Hom.: 0 Cov.: 30 AF XY: 0.00000171 AC XY: 1 AN XY: 583460

African (AFR) AF: 0.00 AC: 0 AN: 23664

American (AMR) AF: 0.00 AC: 0 AN: 10620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17416

East Asian (EAS) AF: 0.00 AC: 0 AN: 27120

South Asian (SAS) AF: 0.00 AC: 0 AN: 50218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3478

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 993530

Other (OTH) AF: 0.00 AC: 0 AN: 49566

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.81
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.061
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.46	T
Polyphen		0.47	P
Vest4		0.20
MutPred		0.29		Gain of MoRF binding (P = 0.0861)
MVP		0.34
MPC		1.1
ClinPred		0.62	D
GERP RS		3.4
Varity_R		0.29
gMVP		0.16
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: rs944923296; hg19: chr11-73019915;