NM_000701.8:c.299_313delTCTCAATGTTACTGT

Variant names:

• chr1-116387400-GGTTCTCAATGTTACT-G
• rs724160008
• NM_000701.8:c.299_313delTCTCAATGTTACTGT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM4 PP3 PP5

The NM_000701.8(ATP1A1):​c.299_313delTCTCAATGTTACTGT​(p.Phe100_Leu104del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. F100F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP1A1 NM_000701.8 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.02
• Publications: 2 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 4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000701.8.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-116387400-GGTTCTCAATGTTACT-G is Pathogenic according to our data. Variant chr1-116387400-GGTTCTCAATGTTACT-G is described in ClinVar as Pathogenic. ClinVar VariationId is 162465.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP1A1	NM_000701.8	c.299_313delTCTCAATGTTACTGT	p.Phe100_Leu104del	disruptive_inframe_deletion	Exon 4 of 23	ENST00000295598.10	NP_000692.2
ATP1A1	NM_001160233.2	c.299_313delTCTCAATGTTACTGT	p.Phe100_Leu104del	disruptive_inframe_deletion	Exon 4 of 23		NP_001153705.1
ATP1A1	NM_001160234.2	c.206_220delTCTCAATGTTACTGT	p.Phe69_Leu73del	disruptive_inframe_deletion	Exon 4 of 23		NP_001153706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP1A1	ENST00000295598.10	c.299_313delTCTCAATGTTACTGT	p.Phe100_Leu104del	disruptive_inframe_deletion	Exon 4 of 23	1	NM_000701.8	ENSP00000295598.5

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Aldosterone-producing adrenal cortex adenoma Pathogenic:1

Feb 17, 2013

Institute of Human Genetics Munich, TUM University Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs724160008; hg19: chr1-116930022; COSMIC: COSV55191965; COSMIC: COSV55191965;