chr2-135651791-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001378107.1(R3HDM1):​c.1787G>A​(p.Gly596Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

R3HDM1
NM_001378107.1 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.857
Variant links:
Genes affected
R3HDM1 (HGNC:9757): (R3H domain containing 1) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10412145).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
R3HDM1NM_001378107.1 linkuse as main transcriptc.1787G>A p.Gly596Asp missense_variant 18/27 ENST00000683871.1 NP_001365036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
R3HDM1ENST00000683871.1 linkuse as main transcriptc.1787G>A p.Gly596Asp missense_variant 18/27 NM_001378107.1 ENSP00000506980 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000936
Hom.:
0

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 submitterclinical testingAmbry GeneticsMay 03, 2023The c.1682G>A (p.G561D) alteration is located in exon 17 (coding exon 15) of the R3HDM1 gene. This alteration results from a G to A substitution at nucleotide position 1682, causing the glycine (G) at amino acid position 561 to be replaced by an aspartic acid (D). 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
Benign
0.19
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.012
.;T;.;.;.
Eigen
Benign
0.054
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.82
.;T;T;D;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.1
.;L;.;.;.
MutationTaster
Benign
1.0
D;D;N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.87
N;N;N;.;N
REVEL
Benign
0.019
Sift
Uncertain
0.0060
D;D;D;.;D
Sift4G
Benign
0.19
T;T;T;T;T
Polyphen
0.030
.;B;.;.;.
Vest4
0.33
MutPred
0.18
.;Loss of glycosylation at S558 (P = 0.081);.;.;.;
MVP
0.54
MPC
0.38
ClinPred
0.45
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.26

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: rs2065177228; hg19: chr2-136409361; API