Variant chr2-38937487-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001145451.5(ARHGEF33):c.718G>C(p.Asp240His) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARHGEF33
NM_001145451.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50

Variant links:

Genes affected

ARHGEF33 (HGNC:37252): (Rho guanine nucleotide exchange factor 33) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF33 links:

LOC105374471 (HGNC:):

LOC105374471 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27157468).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARHGEF33	NM_001145451.5 linkuse as main transcript	c.718G>C	p.Asp240His	missense_variant	9/18	ENST00000409978.7	NP_001138923.2
LOC105374471	XR_939980.3 linkuse as main transcript	n.111-1035C>G		intron_variant, non_coding_transcript_variant
ARHGEF33	NM_001367623.3 linkuse as main transcript	c.718G>C	p.Asp240His	missense_variant	9/19		NP_001354552.1
LOC105374471	XR_001739417.1 linkuse as main transcript	n.113-51C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF33	ENST00000409978.7 linkuse as main transcript	c.718G>C	p.Asp240His	missense_variant	9/18	5	NM_001145451.5	ENSP00000387020	P1	A8MVX0-2
ARHGEF33	ENST00000698009.1 linkuse as main transcript	c.862G>C	p.Asp288His	missense_variant	10/19			ENSP00000513494
ARHGEF33	ENST00000398800.8 linkuse as main transcript	c.718G>C	p.Asp240His	missense_variant	7/16	5		ENSP00000381780	P1	A8MVX0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

156314

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82842

show subpopulations

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 SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399036

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690036

show subpopulations

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:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

The c.718G>C (p.D240H) alteration is located in exon 7 (coding exon 7) of the ARHGEF33 gene. This alteration results from a G to C substitution at nucleotide position 718, causing the aspartic acid (D) at amino acid position 240 to be replaced by a histidine (H). 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

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0080

D;D

Vest4

0.17

MutPred

0.28

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MVP

0.61

ClinPred

0.86

GERP RS

5.6

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over