2-135616692-C-T

Variant summary

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

The NM_001378107.1(R3HDM1):​c.238C>T​(p.Arg80Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,046 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: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

R3HDM1
NM_001378107.1 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03
Variant links:
Genes affected
R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.844

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
R3HDM1NM_001378107.1 linkc.238C>T p.Arg80Trp missense_variant Exon 5 of 27 ENST00000683871.1 NP_001365036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
R3HDM1ENST00000683871.1 linkc.238C>T p.Arg80Trp missense_variant Exon 5 of 27 NM_001378107.1 ENSP00000506980.1 A0A804HIA8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456046
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
724036
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000271
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.238C>T (p.R80W) alteration is located in exon 5 (coding exon 3) of the R3HDM1 gene. This alteration results from a C to T substitution at nucleotide position 238, causing the arginine (R) at amino acid position 80 to be replaced by a tryptophan (W). 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
1.0
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.30
T;.
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.57
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-5.6
D;D
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.99
D;.
Vest4
0.91
MutPred
0.53
Gain of catalytic residue at L78 (P = 0.0032);Gain of catalytic residue at L78 (P = 0.0032);
MVP
0.74
MPC
0.90
ClinPred
1.0
D
GERP RS
5.7
Varity_R
0.77
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.25
Position offset: -24

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: rs1157007126; hg19: chr2-136374262; COSMIC: COSV51520454; COSMIC: COSV51520454; API