rs897301304

Variant names:

• chr16-28903043-C-G
• NM_004320.6:c.2758C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-28903043-C-G
• chr16-28903043-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004320.6(ATP2A1):​c.2758C>G​(p.Gln920Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP2A1 NM_004320.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A1	NM_004320.6	c.2758C>G	p.Gln920Glu	missense_variant	Exon 20 of 23	ENST00000395503.9	NP_004311.1
ATP2A1	NM_173201.5	c.2758C>G	p.Gln920Glu	missense_variant	Exon 20 of 22		NP_775293.1
ATP2A1	NM_001286075.2	c.2383C>G	p.Gln795Glu	missense_variant	Exon 18 of 21		NP_001273004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A1	ENST00000395503.9	c.2758C>G	p.Gln920Glu	missense_variant	Exon 20 of 23	1	NM_004320.6	ENSP00000378879.5
ATP2A1	ENST00000357084.7	c.2758C>G	p.Gln920Glu	missense_variant	Exon 20 of 22	2		ENSP00000349595.3
ATP2A1	ENST00000536376.5	c.2383C>G	p.Gln795Glu	missense_variant	Exon 18 of 21	2		ENSP00000443101.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.75	D;.;.
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Pathogenic	0.68
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.76
MutPred		0.53		Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;
MVP		0.95
MPC		1.3
ClinPred		0.98	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.73
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-28914364;