chr7-144187438-C-A

Variant names:

• chr7-144187438-C-A
• rs996964688
• NM_001003702.3:c.946G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001003702.3(ARHGEF35):​c.946G>T​(p.Gly316Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 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. G316R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF35 NM_001003702.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

Genes affected

ARHGEF35 (HGNC:33846): (Rho guanine nucleotide exchange factor 35)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1616031).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF35	NM_001003702.3	c.946G>T	p.Gly316Cys	missense_variant	Exon 2 of 2	ENST00000378115.3	NP_001003702.2
ARHGEF35	NM_001368318.1	c.946G>T	p.Gly316Cys	missense_variant	Exon 2 of 2		NP_001355247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF35	ENST00000378115.3	c.946G>T	p.Gly316Cys	missense_variant	Exon 2 of 2	1	NM_001003702.3	ENSP00000367355.3
ARHGEF35	ENST00000688754.1	c.946G>T	p.Gly316Cys	missense_variant	Exon 2 of 2			ENSP00000510684.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000109 AC: 1 AN: 915382 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 466410

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: 0.00000152

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.047
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.30
MPC		1.2
ClinPred		0.70	D
GERP RS		-3.4
Varity_R		0.31
gMVP		0.0085

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

Publications

LitVar

Other links and lift over

dbSNP: rs996964688; hg19: chr7-143884531;