12-57273478-G-C

Variant names:

• chr12-57273478-G-C
• rs10783819
• NM_001394031.1:c.1345-3484C>G

Variant summary

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

The NM_001394031.1(R3HDM2):​c.1345-3484C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 152,012 control chromosomes in the GnomAD database, including 15,741 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 0.45 (15741 hom., cov: 31)
• Consequence: R3HDM2 NM_001394031.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 3 publications found

Genes affected

R3HDM2 (HGNC:29167): (R3H domain containing 2) Enables RNA binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258830 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394031.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	NM_001394031.1	MANE Select	c.1345-3484C>G		intron	N/A	NP_001380960.1
	R3HDM2	NM_001351204.2		c.1399-924C>G		intron	N/A	NP_001338133.1
	R3HDM2	NM_001351205.2		c.1399-924C>G		intron	N/A	NP_001338134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	ENST00000402412.6	TSL:1 MANE Select	c.1345-3484C>G		intron	N/A	ENSP00000385839.1
	R3HDM2	ENST00000347140.7	TSL:1	c.1303-3484C>G		intron	N/A	ENSP00000317903.6
	R3HDM2	ENST00000393811.6	TSL:1	n.1139-3484C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67878 AN: 151894 Hom.: 15722 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.447 AC: 67925 AN: 152012 Hom.: 15741 Cov.: 31 AF XY: 0.454 AC XY: 33712 AN XY: 74308

African (AFR) AF: 0.346 AC: 14334 AN: 41450

American (AMR) AF: 0.512 AC: 7816 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2328 AN: 5168

South Asian (SAS) AF: 0.523 AC: 2523 AN: 4824

European-Finnish (FIN) AF: 0.583 AC: 6155 AN: 10560

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32208 AN: 67964

Other (OTH) AF: 0.422 AC: 889 AN: 2106

Alfa AF: 0.336 Hom.: 980

Bravo AF: 0.437

Asia WGS AF: 0.467 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.072
DANN	Benign	0.40
PhyloP100		-0.62
Mutation Taster		=100/0	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: rs10783819; hg19: chr12-57667261;