rs553072768

Variant names:

• chr7-144187099-C-G
• rs553072768
• NM_001003702.3:c.1285G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-144187099-C-G
• chr7-144187099-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003702.3(ARHGEF35):​c.1285G>C​(p.Val429Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 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. V429M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARHGEF35 NM_001003702.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056758016).

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.1285G>C	p.Val429Leu	missense	Exon 2 of 2	NP_001003702.2	A5YM69
	ARHGEF35	NM_001368318.1		c.1285G>C	p.Val429Leu	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.1285G>C	p.Val429Leu	missense	Exon 2 of 2	ENSP00000367355.3	A5YM69
	ARHGEF35	ENST00000688754.1		c.1285G>C	p.Val429Leu	missense	Exon 2 of 2	ENSP00000510684.1	A5YM69
	ARHGEF35	ENST00000852510.1		c.1285G>C	p.Val429Leu	missense	Exon 3 of 3	ENSP00000522569.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.00000447 AC: 1 AN: 223632 AF XY: 0.00000821

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000214 AC: 3 AN: 1399240 Hom.: 0 Cov.: 31 AF XY: 0.00000287 AC XY: 2 AN XY: 696672

African (AFR) AF: 0.00 AC: 0 AN: 32318

American (AMR) AF: 0.00 AC: 0 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25768

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058086

Other (OTH) AF: 0.00 AC: 0 AN: 58286

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.040
DANN	Benign	0.82
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.22
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.0060
Sift	Benign	0.32	T
Sift4G	Benign	0.59	T
Polyphen		0.034	B
Vest4		0.035
MutPred		0.24		Loss of sheet (P = 0.0104)
MVP		0.040
MPC		1.1
ClinPred		0.029	T
GERP RS		-3.3
Varity_R		0.044
gMVP		0.016
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

dbSNP: rs553072768; hg19: chr7-143884192;