1-116384035-C-T

Variant names:

• chr1-116384035-C-T
• NM_000701.8:c.34C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000701.8(ATP1A1):​c.34C>T​(p.Pro12Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P12P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP1A1 NM_000701.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

ATP1A1 (HGNC:799): (ATPase Na+/K+ transporting subunit alpha 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+ -ATPases. Na+/K+ -ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes an alpha 1 subunit. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ATP1A1-AS1 (HGNC:28262): (ATP1A1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3309189).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000701.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	NM_000701.8	MANE Select	c.34C>T	p.Pro12Ser	missense	Exon 2 of 23	NP_000692.2
	ATP1A1	NM_001160233.2		c.34C>T	p.Pro12Ser	missense	Exon 2 of 23	NP_001153705.1	P05023-4
	ATP1A1	NM_001160234.2		c.-60C>T		5_prime_UTR	Exon 2 of 23	NP_001153706.1	P05023-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A1	ENST00000295598.10	TSL:1 MANE Select	c.34C>T	p.Pro12Ser	missense	Exon 2 of 23	ENSP00000295598.5	P05023-1
	ATP1A1	ENST00000897942.1		c.34C>T	p.Pro12Ser	missense	Exon 2 of 24	ENSP00000568001.1
	ATP1A1	ENST00000945201.1		c.34C>T	p.Pro12Ser	missense	Exon 2 of 23	ENSP00000615260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.051
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.6	L
PhyloP100		5.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.33	N
REVEL	Uncertain	0.41
Sift	Benign	0.61	T
Sift4G	Benign	0.73	T
Polyphen		0.0020	B
Vest4		0.50
MutPred		0.16		Gain of phosphorylation at P12 (P = 0.0079)
MVP		0.78
MPC		1.4
ClinPred		0.83	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.22
Mutation Taster		=195/105	polymorphism

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

Other links and lift over

hg19: chr1-116926657;