12-57269059-G-A

Variant names:

• chr12-57269059-G-A
• rs1438737313
• NM_001394031.1:c.1738C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001394031.1(R3HDM2):​c.1738C>T​(p.Gln580*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: R3HDM2 NM_001394031.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.60
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1738C>T	p.Gln580*	stop_gained	Exon 17 of 24	NP_001380960.1	B5MCU0
	R3HDM2	NM_001351204.2		c.1894C>T	p.Gln632*	stop_gained	Exon 19 of 26	NP_001338133.1
	R3HDM2	NM_001351205.2		c.1894C>T	p.Gln632*	stop_gained	Exon 18 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.1738C>T	p.Gln580*	stop_gained	Exon 17 of 24	ENSP00000385839.1	B5MCU0
	R3HDM2	ENST00000347140.7	TSL:1	c.1696C>T	p.Gln566*	stop_gained	Exon 17 of 24	ENSP00000317903.6	Q9Y2K5-1
	R3HDM2	ENST00000393811.6	TSL:1	n.1532C>T		non_coding_transcript_exon	Exon 7 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		9.6
Vest4		0.49
GERP RS		5.1
Mutation Taster		=5/195	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1438737313; hg19: chr12-57662842;