16-28878165-C-T

Variant names:

• chr16-28878165-C-T
• rs3888190
• ENST00000691192.2:n.1772G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000691192.2(ATP2A1-AS1):​n.1772G>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 0.00000666 in 150,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 (0 hom., cov: 28)
• Consequence: ATP2A1-AS1 ENST00000691192.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 115 publications found

Genes affected

ATP2A1-AS1 (HGNC:51370): (ATP2A1 antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• Brody myopathy

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A1-AS1	ENST00000691192.2	n.1772G>A		non_coding_transcript_exon_variant	Exon 1 of 1
ATP2A1	ENST00000357084.7	c.-507C>T		upstream_gene_variant		2		ENSP00000349595.3

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150136 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150136 Hom.: 0 Cov.: 28 AF XY: 0.0000137 AC XY: 1 AN XY: 73124

African (AFR) AF: 0.0000246 AC: 1 AN: 40606

American (AMR) AF: 0.00 AC: 0 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67598

Other (OTH) AF: 0.00 AC: 0 AN: 2062

Alfa AF: 0.00 Hom.: 25705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-1.5
PromoterAI		-0.0052	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3888190; hg19: chr16-28889486;