NM_014578.4:c.53T>G

Variant names:

• chr11-67056955-T-G
• rs375849783
• NM_014578.4:c.53T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014578.4(RHOD):​c.53T>G​(p.Val18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,345,416 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: RHOD NM_014578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHOD	NM_014578.4	c.53T>G	p.Val18Gly	missense_variant	Exon 1 of 5	ENST00000308831.7	NP_055393.1
RHOD	NM_001300886.2	c.53T>G	p.Val18Gly	missense_variant	Exon 1 of 3		NP_001287815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHOD	ENST00000308831.7	c.53T>G	p.Val18Gly	missense_variant	Exon 1 of 5	1	NM_014578.4	ENSP00000308576.2
RHOD	ENST00000532559.1	c.53T>G	p.Val18Gly	missense_variant	Exon 1 of 3	3		ENSP00000432003.1
RHOD	ENST00000533360.2	n.96T>G		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1345416 Hom.: 0 Cov.: 31 AF XY: 0.00000150 AC XY: 1 AN XY: 664474

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000337

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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.098	.;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.46	.;T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.77	T
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Vest4		0.56
MutPred		0.73		Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);
MVP		0.43
MPC		0.85
ClinPred		0.17	T
GERP RS		0.94
gMVP		0.57

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

Other links and lift over

dbSNP: rs375849783; hg19: chr11-66824426;