7-144187189-C-T

Variant names:

• chr7-144187189-C-T
• NM_001003702.3:c.1195G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001003702.3(ARHGEF35):​c.1195G>A​(p.Glu399Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 19)
• Consequence: ARHGEF35 NM_001003702.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.830
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046495706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003702.3. 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
	ARHGEF35	NM_001003702.3	MANE Select	c.1195G>A	p.Glu399Lys	missense	Exon 2 of 2	NP_001003702.2	A5YM69
	ARHGEF35	NM_001368318.1		c.1195G>A	p.Glu399Lys	missense	Exon 2 of 2	NP_001355247.1	A5YM69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF35	ENST00000378115.3	TSL:1 MANE Select	c.1195G>A	p.Glu399Lys	missense	Exon 2 of 2	ENSP00000367355.3	A5YM69
	ARHGEF35	ENST00000688754.1		c.1195G>A	p.Glu399Lys	missense	Exon 2 of 2	ENSP00000510684.1	A5YM69
	ARHGEF35	ENST00000852510.1		c.1195G>A	p.Glu399Lys	missense	Exon 3 of 3	ENSP00000522569.1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.83
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.0070
Sift	Benign	0.094	T
Sift4G	Uncertain	0.017	D
Polyphen		0.087	B
Vest4		0.11
MutPred		0.25		Gain of ubiquitination at E399 (P = 0.0029)
MVP		0.040
MPC		1.3
ClinPred		0.10	T
GERP RS		-1.1
Varity_R		0.059
gMVP		0.018
Mutation Taster		=100/0	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

hg19: chr7-143884282;