Variant chr11-67066828-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000308831.7(RHOD):c.311T>G(p.Phe104Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

RHOD
ENST00000308831.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.919

Variant links:

Genes affected

RHOD (HGNC:670): (ras homolog family member D) Ras homolog, or Rho, proteins interact with protein kinases and may serve as targets for activated GTPase. They play a critical role in muscle differentiation. The protein encoded by this gene binds GTP and is a member of the small GTPase superfamily. It is involved in endosome dynamics and reorganization of the actin cytoskeleton, and it may coordinate membrane transport with the function of the cytoskeleton. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

RHOD links:

RHOD (HGNC:):

RHOD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOD	NM_014578.4 linkuse as main transcript	c.311T>G	p.Phe104Cys	missense_variant	3/5	ENST00000308831.7	NP_055393.1	O00212
RHOD	NM_001300886.2 linkuse as main transcript	c.133-3597T>G		intron_variant			NP_001287815.1	E9PIG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHOD	ENST00000308831.7 linkuse as main transcript	c.311T>G	p.Phe104Cys	missense_variant	3/5	1	NM_014578.4	ENSP00000308576.2	O00212
RHOD	ENST00000532559.1 linkuse as main transcript	c.133-3597T>G		intron_variant		3		ENSP00000432003.1	E9PIG5
RHOD	ENST00000533360.2 linkuse as main transcript	n.354T>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251394

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460754

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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

Jun 27, 2022

The c.311T>G (p.F104C) alteration is located in exon 3 (coding exon 3) of the RHOD gene. This alteration results from a T to G substitution at nucleotide position 311, causing the phenylalanine (F) at amino acid position 104 to be replaced by a cysteine (C). 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.89

M_CAP

Pathogenic

0.32

MetaRNN

Pathogenic

0.89

MetaSVM

Pathogenic

0.80

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Vest4

0.75

MVP

0.95

MPC

1.8

ClinPred

0.98

GERP RS

4.6

gMVP

0.66

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

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