rs2305165

Variant names:

• chr2-135652004-A-C
• rs2305165
• NM_001378107.1:c.2000A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-135652004-A-C
• chr2-135652004-A-G
• chr2-135652004-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378107.1(R3HDM1):​c.2000A>C​(p.Gln667Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,604,660 control chromosomes in the GnomAD database, including 11,409 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1274 hom., cov: 32)
  • Exomes 𝑓: 0.098 (10135 hom.)
• Consequence: R3HDM1 NM_001378107.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.97
• Publications: 22 publications found

Genes affected

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

ENSG00000308733 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016035736).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

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.2000A>C	p.Gln667Pro	missense	Exon 18 of 27	NP_001365036.1	A0A804HIA8
	R3HDM1	NM_001282798.2		c.1898A>C	p.Gln633Pro	missense	Exon 17 of 26	NP_001269727.1	Q15032-3
	R3HDM1	NM_001354200.2		c.1898A>C	p.Gln633Pro	missense	Exon 17 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.2000A>C	p.Gln667Pro	missense	Exon 18 of 27	ENSP00000506980.1	A0A804HIA8
	R3HDM1	ENST00000264160.8	TSL:1	c.1895A>C	p.Gln632Pro	missense	Exon 17 of 26	ENSP00000264160.4	Q15032-1
	R3HDM1	ENST00000409478.5	TSL:1	c.1511A>C	p.Gln504Pro	missense	Exon 14 of 23	ENSP00000386457.1	Q15032-2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17657 AN: 152052 Hom.: 1278 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.0838

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.140 AC: 33618 AN: 239464 AF XY: 0.145

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.167

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.0879

Gnomad OTH exome AF: 0.134

GnomAD4 exome AF: 0.0976 AC: 141831 AN: 1452490 Hom.: 10135 Cov.: 34 AF XY: 0.104 AC XY: 74882 AN XY: 721464

African (AFR) AF: 0.117 AC: 3896 AN: 33424

American (AMR) AF: 0.204 AC: 9067 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2856 AN: 25224

East Asian (EAS) AF: 0.172 AC: 6803 AN: 39622

South Asian (SAS) AF: 0.289 AC: 24311 AN: 84206

European-Finnish (FIN) AF: 0.104 AC: 5526 AN: 52926

Middle Eastern (MID) AF: 0.302 AC: 1719 AN: 5698

European-Non Finnish (NFE) AF: 0.0733 AC: 81187 AN: 1106960

Other (OTH) AF: 0.108 AC: 6466 AN: 60046

GnomAD4 genome AF: 0.116 AC: 17662 AN: 152170 Hom.: 1274 Cov.: 32 AF XY: 0.123 AC XY: 9169 AN XY: 74392

African (AFR) AF: 0.111 AC: 4602 AN: 41508

American (AMR) AF: 0.195 AC: 2982 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 377 AN: 3466

East Asian (EAS) AF: 0.168 AC: 869 AN: 5188

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4814

European-Finnish (FIN) AF: 0.110 AC: 1163 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.0838 AC: 5699 AN: 68010

Other (OTH) AF: 0.137 AC: 290 AN: 2114

Alfa AF: 0.0978 Hom.: 3952

Bravo AF: 0.117

TwinsUK AF: 0.0717 AC: 266

ALSPAC AF: 0.0659 AC: 254

ESP6500AA AF: 0.112 AC: 495

ESP6500EA AF: 0.0829 AC: 713

ExAC AF: 0.137 AC: 16625

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.35
MPC		0.39
ClinPred		0.065	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.52
Mutation Taster		=60/40	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2305165; hg19: chr2-136409574; COSMIC: COSV51524836; COSMIC: COSV51524836;