4-40243500-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_004310.5(RHOH):​c.114C>G​(p.Tyr38*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. Y38Y) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Consequence

RHOH
NM_004310.5 stop_gained

Scores

2
1
4

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.954
Variant links:
Genes affected
RHOH (HGNC:686): (ras homolog family member H) The protein encoded by this gene is a member of the Ras superfamily of guanosine triphosphate (GTP)-metabolizing enzymes. The encoded protein is expressed in hematopoietic cells, where it functions as a negative regulator of cell growth and survival. This gene may be hypermutated or misexpressed in leukemias and lymphomas. Chromosomal translocations in non-Hodgkin's lymphoma occur between this locus and B-cell CLL/lymphoma 6 (BCL6) on chromosome 3, leading to the production of fusion transcripts. Alternative splicing in the 5' untranslated region results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-40243500-C-G is Pathogenic according to our data. Variant chr4-40243500-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 617610.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHOHNM_004310.5 linkc.114C>G p.Tyr38* stop_gained Exon 3 of 3 ENST00000381799.10 NP_004301.1 Q15669Q6ICP4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOHENST00000381799.10 linkc.114C>G p.Tyr38* stop_gained Exon 3 of 3 1 NM_004310.5 ENSP00000371219.4 Q15669

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Epidermodysplasia verruciformis, susceptibility to, 4 Pathogenic:1
Dec 06, 2024
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.48
CADD
Benign
20
DANN
Uncertain
0.99
Eigen
Benign
0.012
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.31
N
Vest4
0.78
GERP RS
-6.1

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.

Other links and lift over

dbSNP: rs773779601; hg19: chr4-40245120; API