7-144187549-C-T

Position:

• chr7-144187549-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003702.3(ARHGEF35):​c.835G>A​(p.Val279Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.0000032 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF35 NM_001003702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0570

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023679256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF35	NM_001003702.3	c.835G>A	p.Val279Ile	missense_variant	2/2	ENST00000378115.3	NP_001003702.2
ARHGEF35	NM_001368318.1	c.835G>A	p.Val279Ile	missense_variant	2/2		NP_001355247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF35	ENST00000378115.3	c.835G>A	p.Val279Ile	missense_variant	2/2	1	NM_001003702.3	ENSP00000367355.3
ARHGEF35	ENST00000688754.1	c.835G>A	p.Val279Ile	missense_variant	2/2			ENSP00000510684.1

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000316 AC: 4 AN: 1267278 Hom.: 1 Cov.: 26 AF XY: 0.00000157 AC XY: 1 AN XY: 637740

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: 0.00000426

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.835G>A (p.V279I) alteration is located in exon 2 (coding exon 1) of the ARHGEF35 gene. This alteration results from a G to A substitution at nucleotide position 835, causing the valine (V) at amino acid position 279 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.9
DANN	Benign	0.88
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.085
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Polyphen		0.0060	B
Vest4		0.032
MutPred		0.18		Gain of catalytic residue at L284 (P = 0.0381);
MVP		0.17
MPC		0.96
ClinPred		0.031	T
GERP RS		-3.6
Varity_R		0.026
gMVP		0.0035

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143884642;