12-57266789-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HDM2	NM_001394031.1	c.2073C>T	p.Tyr691Tyr	synonymous_variant	Exon 19 of 24	ENST00000402412.6	NP_001380960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HDM2	ENST00000402412.6	c.2073C>T	p.Tyr691Tyr	synonymous_variant	Exon 19 of 24	1	NM_001394031.1	ENSP00000385839.1
ENSG00000258830	ENST00000548184.1	n.*1123C>T		non_coding_transcript_exon_variant	Exon 9 of 15	2		ENSP00000477227.1
ENSG00000258830	ENST00000548184.1	n.*1123C>T		3_prime_UTR_variant	Exon 9 of 15	2		ENSP00000477227.1

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

GnomAD3 exomes AF: 0.00249 AC: 623 AN: 250142 Hom.: 18 AF XY: 0.00186 AC XY: 251 AN XY: 135212

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.0354

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.00141

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

Gnomad4 AFR AF: 0.0359

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00479 Hom.: 2

Bravo AF: 0.0109

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.7
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs146780443; hg19: chr12-57660572;