Genetic Variant ARHGEF37:p.Arg59Pro (chr5-149597945-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001669.3(ARHGEF37):c.176G>C(p.Arg59Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R59C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ARHGEF37
NM_001001669.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

1 publications found

Variant links:

Genes affected

ARHGEF37 (HGNC:34430): (Rho guanine nucleotide exchange factor 37) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF37 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11655486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF37	NM_001001669.3 link	c.176G>C	p.Arg59Pro	missense_variant	Exon 2 of 13	ENST00000333677.7	NP_001001669.2	A1IGU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF37	ENST00000333677.7 link	c.176G>C	p.Arg59Pro	missense_variant	Exon 2 of 13	2	NM_001001669.3	ENSP00000328083.6		A1IGU5
ARHGEF37	ENST00000505810.5 link	c.176G>C	p.Arg59Pro	missense_variant	Exon 2 of 3	5		ENSP00000425621.1		D6RJH4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

206780

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32530

American (AMR)

AF:

0.00

AC:

AN:

40308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25548

East Asian (EAS)

AF:

0.00

AC:

AN:

38142

South Asian (SAS)

AF:

0.00

AC:

AN:

81982

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100468

Other (OTH)

AF:

0.00

AC:

AN:

59490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.0057

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.87

D;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.67

.;N

PhyloP100

0.034

PrimateAI

Benign

0.21

PROVEAN

Benign

2.3

N;N

REVEL

Uncertain

0.31

Sift

Benign

0.21

T;T

Sift4G

Uncertain

0.041

D;T

Polyphen

0.16

.;B

Vest4

0.58

MutPred

0.68

Loss of solvent accessibility (P = 0.1077);Loss of solvent accessibility (P = 0.1077);

MVP

0.12

MPC

0.49

ClinPred

0.61

GERP RS

-0.045

Varity_R

0.22

gMVP

0.41

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over