rs768494805

Variant names:

• chr13-111205290-C-A
• NM_001354046.2:c.254C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-111205290-C-A
• chr13-111205290-C-G
• chr13-111205290-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001354046.2(ARHGEF7):​c.254C>A​(p.Thr85Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000691 in 1,447,096 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. 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. T85M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARHGEF7 NM_001354046.2 missense, splice_region
• Scores: Splicing: ADA: 0.9924
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.71

Genes affected

ARHGEF7 (HGNC:15607): (Rho guanine nucleotide exchange factor 7) This gene encodes a protein that belongs to a family of cytoplasmic proteins that activate the Ras-like family of Rho proteins by exchanging bound GDP for GTP. It forms a complex with the small GTP binding protein Rac1 and recruits Rac1 to membrane ruffles and to focal adhesions. Multiple alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF7	NM_001354046.2	c.254C>A	p.Thr85Lys	missense_variant, splice_region_variant	Exon 3 of 22	ENST00000646102.2	NP_001340975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF7	ENST00000646102.2	c.254C>A	p.Thr85Lys	missense_variant, splice_region_variant	Exon 3 of 22		NM_001354046.2	ENSP00000495631.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447096 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.36	.;.;T;.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.56	T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.50	T;D;D;T;T
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Uncertain	2.6	.;.;M;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.80	N;N;N;.;N
REVEL	Benign	0.23
Sift	Benign	0.10	T;T;T;.;D
Sift4G	Benign	0.26	T;T;T;.;T
Polyphen		0.90	P;D;P;.;.
Vest4		0.58
MutPred		0.52		.;.;Gain of ubiquitination at T106 (P = 0.0211);.;.;
MVP		0.82
MPC		1.7
ClinPred		0.83	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.74
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: -1

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: chr13-111857637;