rs34088964

Variant names:

• chr2-135638642-A-C
• rs34088964
• NM_001378107.1:c.928A>C
• R3HDM1 p.Ile310Leu

Your query was ambiguous. Multiple possible variants found:

• chr2-135638642-A-C
• chr2-135638642-A-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001378107.1(R3HDM1):​c.928A>C​(p.Ile310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,610,556 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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: 𝑓 0.00044 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 3 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018303633).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378107.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	NM_001378107.1	MANE Select	c.928A>C	p.Ile310Leu	missense	Exon 12 of 27	NP_001365036.1	A0A804HIA8
	R3HDM1	NM_001282798.2		c.928A>C	p.Ile310Leu	missense	Exon 12 of 26	NP_001269727.1	Q15032-3
	R3HDM1	NM_001354200.2		c.928A>C	p.Ile310Leu	missense	Exon 12 of 26	NP_001341129.1	Q15032-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM1	ENST00000683871.1	MANE Select	c.928A>C	p.Ile310Leu	missense	Exon 12 of 27	ENSP00000506980.1	A0A804HIA8
	R3HDM1	ENST00000264160.8	TSL:1	c.928A>C	p.Ile310Leu	missense	Exon 12 of 26	ENSP00000264160.4	Q15032-1
	R3HDM1	ENST00000409478.5	TSL:1	c.796A>C	p.Ile266Leu	missense	Exon 10 of 23	ENSP00000386457.1	Q15032-2

Frequencies

GnomAD3 genomes AF: 0.000440 AC: 67 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000823

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000474 AC: 119 AN: 251198 AF XY: 0.000435

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000942

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.00101 AC: 1468 AN: 1458402 Hom.: 2 Cov.: 31 AF XY: 0.000942 AC XY: 684 AN XY: 725804

African (AFR) AF: 0.000180 AC: 6 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86170

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00127 AC: 1410 AN: 1108986

Other (OTH) AF: 0.000664 AC: 40 AN: 60270

GnomAD4 genome AF: 0.000440 AC: 67 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 30 AN XY: 74326

African (AFR) AF: 0.000193 AC: 8 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000823 AC: 56 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000810 Hom.: 0

Bravo AF: 0.000453

EpiCase AF: 0.000709

EpiControl AF: 0.000948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.62
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.96	N
PhyloP100		3.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	0.78	T
PromoterAI		-0.017	Neutral
Varity_R		0.065
gMVP		0.093
Mutation Taster		=95/5	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34088964;

hg19: chr2-136396212;