2-135641560-G-C

Variant summary

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

The NM_001378107.1(R3HDM1):c.1244G>C(p.Gly415Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.64

Genes affected

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

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/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.1244G>C	p.Gly415Ala	missense_variant	15/27	ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.1244G>C	p.Gly415Ala	missense_variant	15/27		NM_001378107.1	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 08, 2023

The c.1244G>C (p.G415A) alteration is located in exon 15 (coding exon 13) of the R3HDM1 gene. This alteration results from a G to C substitution at nucleotide position 1244, causing the glycine (G) at amino acid position 415 to be replaced by an alanine (A). 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	0.25
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
Cadd	Pathogenic	32
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.7	L;.;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.095	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.82
MutPred		0.20		Gain of glycosylation at S410 (P = 0.1675);.;Gain of glycosylation at S410 (P = 0.1675);
MVP		0.60
MPC		0.92
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: 44

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-136399130;