NM_001036.6:c.2784-10T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001036.6(RYR3):c.2784-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,543,082 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 11 hom. )

Consequence

RYR3
NM_001036.6 intron

Scores

Splicing: ADA: 0.009634

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.08

Publications

0 publications found

Variant links:

Genes affected

RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

RYR3 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen, G2P
congenital myopathy
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

RYR3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-33631200-T-G is Benign according to our data. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-33631200-T-G is described in CliVar as Benign. Clinvar id is 531146.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR3	NM_001036.6 link	c.2784-10T>G		intron_variant	Intron 22 of 103	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RYR3	ENST00000634891.2 link	c.2784-10T>G	intron_variant	Intron 22 of 103	1	NM_001036.6	ENSP00000489262.1	Q15413-1
RYR3	ENST00000389232.9 link	c.2784-10T>G	intron_variant	Intron 22 of 103	5		ENSP00000373884.5	A0A0X1KG73
RYR3	ENST00000415757.7 link	c.2784-10T>G	intron_variant	Intron 22 of 102	2		ENSP00000399610.3	Q15413-2
RYR3	ENST00000634418.1 link	c.2784-10T>G	intron_variant	Intron 22 of 101	5		ENSP00000489529.1	A0A0U1RRH1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00133

AC:

253

AN:

190478

AF XY:

0.00191

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000363

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.000621

AC:

863

AN:

1390776

Hom.:

Cov.:

AF XY:

0.000935

AC XY:

645

AN XY:

689880

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31890

American (AMR)

AF:

0.0000523

AC:

AN:

38270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25106

East Asian (EAS)

AF:

0.00

AC:

AN:

37914

South Asian (SAS)

AF:

0.0103

AC:

820

AN:

79512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51178

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1063242

Other (OTH)

AF:

0.000638

AC:

AN:

58014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000407

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0126

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.0000416

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Dec 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.8

(source)

DANN

Benign

0.68

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0096

dbscSNV1_RF

Benign

0.21

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over