rs146780443

Variant names:

• chr12-57266789-G-A
• rs146780443
• NM_001394031.1:c.2073C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57266789-G-A
• chr12-57266789-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001394031.1(R3HDM2):​c.2073C>T​(p.Tyr691Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,611,002 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (28 hom.)
• Consequence: R3HDM2 NM_001394031.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.847
• Publications: 0 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 12-57266789-G-A is Benign according to our data. Variant chr12-57266789-G-A is described in ClinVar as Benign. ClinVar VariationId is 781083.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.847 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1536/152316) while in subpopulation AFR AF = 0.0359 (1491/41562). AF 95% confidence interval is 0.0344. There are 17 homozygotes in GnomAd4. There are 723 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	NM_001394031.1	MANE Select	c.2073C>T	p.Tyr691Tyr	synonymous	Exon 19 of 24	NP_001380960.1	B5MCU0
	R3HDM2	NM_001351204.2		c.2229C>T	p.Tyr743Tyr	synonymous	Exon 21 of 26	NP_001338133.1
	R3HDM2	NM_001351205.2		c.2229C>T	p.Tyr743Tyr	synonymous	Exon 20 of 25	NP_001338134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDM2	ENST00000402412.6	TSL:1 MANE Select	c.2073C>T	p.Tyr691Tyr	synonymous	Exon 19 of 24	ENSP00000385839.1	B5MCU0
	R3HDM2	ENST00000347140.7	TSL:1	c.2031C>T	p.Tyr677Tyr	synonymous	Exon 19 of 24	ENSP00000317903.6	Q9Y2K5-1
	R3HDM2	ENST00000393811.6	TSL:1	n.1867C>T		non_coding_transcript_exon	Exon 9 of 14

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1536 AN: 152198 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00249 AC: 623 AN: 250142 AF XY: 0.00186

Gnomad AFR exome AF: 0.0358

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000914 AC: 1333 AN: 1458686 Hom.: 28 Cov.: 30 AF XY: 0.000765 AC XY: 555 AN XY: 725806

African (AFR) AF: 0.0354 AC: 1183 AN: 33372

American (AMR) AF: 0.00114 AC: 51 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000929 AC: 8 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109344

Other (OTH) AF: 0.00141 AC: 85 AN: 60256

GnomAD4 genome AF: 0.0101 AC: 1536 AN: 152316 Hom.: 17 Cov.: 32 AF XY: 0.00971 AC XY: 723 AN XY: 74482

African (AFR) AF: 0.0359 AC: 1491 AN: 41562

American (AMR) AF: 0.00209 AC: 32 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00461 Hom.: 6

Bravo AF: 0.0109

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.7
DANN	Benign	0.77
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146780443; hg19: chr12-57660572;