Genetic Variant RYR3-DT:n.178C>A (chr15-33306336-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000561458.5(RYR3-DT):n.193C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,926 control chromosomes in the GnomAD database, including 18,624 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 0.49 ( 18624 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

RYR3-DT
ENST00000561458.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.78

Variant links:

Genes affected

RYR3-DT (HGNC:51417): (RYR3 divergent transcript)

RYR3-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3-DT	NR_120326.1 link	n.192C>A		non_coding_transcript_exon_variant	Exon 2 of 3
RYR3-DT	NR_120327.1 link	n.178C>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
RYR3-DT	ENST00000559457.1 link	n.178C>A	non_coding_transcript_exon_variant	Exon 2 of 3	3
RYR3-DT	ENST00000561458.5 link	n.193C>A	non_coding_transcript_exon_variant	Exon 2 of 3	2
RYR3-DT	ENST00000666561.1 link	n.311C>A	non_coding_transcript_exon_variant	Exon 2 of 3
RYR3-DT	ENST00000653439.1 link	n.289+3814C>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74851

AN:

151808

Hom.:

18634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.479

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.508

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.515

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.493

AC:

74858

AN:

151926

Hom.:

18624

Cov.:

AF XY:

0.494

AC XY:

36699

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.458

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.496

Gnomad4 SAS

AF:

0.518

Gnomad4 FIN

AF:

0.508

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.513

Alfa

AF:

0.502

Hom.:

25325

Bravo

AF:

0.490

Asia WGS

AF:

0.492

AC:

1717

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.18

DANN

Benign

0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over