2-135638642-A-G

Position:

• chr2-135638642-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378107.1(R3HDM1):​c.928A>G​(p.Ile310Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09092051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HDM1	NM_001378107.1	c.928A>G	p.Ile310Val	missense_variant	12/27	ENST00000683871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HDM1	ENST00000683871.1	c.928A>G	p.Ile310Val	missense_variant	12/27		NM_001378107.1	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458408 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725808

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.011	.;T;.;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.091	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.060	.;N;.;.;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.69	N;N;N;.;N
REVEL	Benign	0.027
Sift	Benign	0.20	T;T;T;.;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.048	.;B;.;.;.
Vest4		0.20
MutPred		0.29		.;Loss of catalytic residue at L315 (P = 0.0362);.;.;Loss of catalytic residue at L315 (P = 0.0362);
MVP		0.23
MPC		0.22
ClinPred		0.66	D
GERP RS		4.3
Varity_R		0.041
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34088964; hg19: chr2-136396212;