chr11-73308840-G-T

Variant names:

• chr11-73308840-G-T
• rs920266362
• NM_014786.4:c.202G>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.202G>T​(p.Ala68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000761 in 1,182,952 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. A68T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: ARHGEF17 NM_014786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 1 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=0.10140365).

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.202G>T	p.Ala68Ser	missense	Exon 1 of 21	NP_055601.2
	ARHGEF17-AS1	NR_147696.1		n.522C>A		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.202G>T	p.Ala68Ser	missense	Exon 1 of 21	ENSP00000263674.3	Q96PE2
	ARHGEF17	ENST00000914587.1		c.202G>T	p.Ala68Ser	missense	Exon 1 of 20	ENSP00000584647.1
	ARHGEF17-AS1	ENST00000546324.1	TSL:2	n.522C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000761 AC: 9 AN: 1182952 Hom.: 0 Cov.: 30 AF XY: 0.00000350 AC XY: 2 AN XY: 570752

African (AFR) AF: 0.00 AC: 0 AN: 23376

American (AMR) AF: 0.00 AC: 0 AN: 8904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16334

East Asian (EAS) AF: 0.00 AC: 0 AN: 26946

South Asian (SAS) AF: 0.00 AC: 0 AN: 45940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3336

European-Non Finnish (NFE) AF: 0.00000815 AC: 8 AN: 981458

Other (OTH) AF: 0.0000206 AC: 1 AN: 48468

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.41
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.12	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.36	T
Polyphen		0.088	B
Vest4		0.095
MutPred		0.21		Gain of phosphorylation at A68 (P = 0.0124)
MVP		0.29
MPC		0.39
ClinPred		0.13	T
GERP RS		0.47
Varity_R		0.21
gMVP		0.20
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: rs920266362; hg19: chr11-73019885;