Variant chr16-28898456-GC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_004320.6(ATP2A1):c.1764+6del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,612,294 control chromosomes in the GnomAD database, including 1,955 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 849 hom., cov: 31)

Exomes 𝑓: 0.014 ( 1106 hom. )

Consequence

ATP2A1
NM_004320.6 splice_donor_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.108

Variant links:

Genes affected

ATP2A1 (HGNC:811): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Oct 2013]

ATP2A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 16-28898456-GC-G is Benign according to our data. Variant chr16-28898456-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 96541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ATP2A1	NM_004320.6 linkuse as main transcript	c.1764+6del	splice_donor_region_variant, intron_variant	ENST00000395503.9	NP_004311.1
ATP2A1	NM_001286075.2 linkuse as main transcript	c.1389+6del	splice_donor_region_variant, intron_variant		NP_001273004.1
ATP2A1	NM_173201.5 linkuse as main transcript	c.1764+6del	splice_donor_region_variant, intron_variant		NP_775293.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ATP2A1	ENST00000395503.9 linkuse as main transcript	c.1764+6del	splice_donor_region_variant, intron_variant	1	NM_004320.6	ENSP00000378879	P4	O14983-2
ATP2A1	ENST00000357084.7 linkuse as main transcript	c.1764+6del	splice_donor_region_variant, intron_variant	2		ENSP00000349595	A1	O14983-1
ATP2A1	ENST00000536376.5 linkuse as main transcript	c.1389+6del	splice_donor_region_variant, intron_variant	2		ENSP00000443101		O14983-3
ATP2A1	ENST00000564732.1 linkuse as main transcript	c.*407+6del	splice_donor_region_variant, intron_variant, NMD_transcript_variant	5		ENSP00000457357

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9692

AN:

152158

Hom.:

848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00614

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0312

AC:

7554

AN:

242494

Hom.:

512

AF XY:

0.0258

AC XY:

3413

AN XY:

132148

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.00780

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.00297

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.00597

Gnomad OTH exome

AF:

0.0251

GnomAD4 exome

AF:

0.0137

AC:

19997

AN:

1460018

Hom.:

1106

Cov.:

AF XY:

0.0128

AC XY:

9302

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.00751

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.0181

Gnomad4 NFE exome

AF:

0.00437

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0638

AC:

9711

AN:

152276

Hom.:

849

Cov.:

AF XY:

0.0622

AC XY:

4629

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.00613

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.00761

Hom.:

Bravo

AF:

0.0702

Asia WGS

AF:

0.0680

AC:

235

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Brody myopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 15, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over