1-160155152-C-T

Variant names:

• chr1-160155152-C-T
• rs140019547
• NM_144699.4:c.315C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_144699.4(ATP1A4):​c.315C>T​(p.Phe105Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,605,162 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (3 hom., cov: 30)
  • Exomes 𝑓: 0.00054 (8 hom.)
• Consequence: ATP1A4 NM_144699.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.51
• Publications: 1 publications found

Genes affected

ATP1A4 (HGNC:14073): (ATPase Na+/K+ transporting subunit alpha 4) 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 4 subunit. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-160155152-C-T is Benign according to our data. Variant chr1-160155152-C-T is described in ClinVar as Benign. ClinVar VariationId is 790492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.51 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00539 (812/150630) while in subpopulation AFR AF = 0.0189 (773/40982). AF 95% confidence interval is 0.0178. There are 3 homozygotes in GnomAd4. There are 396 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144699.4. 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
	ATP1A4	NM_144699.4	MANE Select	c.315C>T	p.Phe105Phe	synonymous	Exon 3 of 22	NP_653300.2	Q13733-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1A4	ENST00000368081.9	TSL:1 MANE Select	c.315C>T	p.Phe105Phe	synonymous	Exon 3 of 22	ENSP00000357060.4	Q13733-1
	ATP1A4	ENST00000477338.5	TSL:1	n.315C>T		non_coding_transcript_exon	Exon 3 of 22	ENSP00000434272.1	E9PRA5

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 810 AN: 150520 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00173

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00385

GnomAD2 exomes AF: 0.00135 AC: 339 AN: 251400 AF XY: 0.00104

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000541 AC: 787 AN: 1454532 Hom.: 8 Cov.: 35 AF XY: 0.000449 AC XY: 325 AN XY: 723874

African (AFR) AF: 0.0195 AC: 650 AN: 33302

American (AMR) AF: 0.000650 AC: 29 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39562

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53010

Middle Eastern (MID) AF: 0.000871 AC: 5 AN: 5740

European-Non Finnish (NFE) AF: 0.0000235 AC: 26 AN: 1106130

Other (OTH) AF: 0.00105 AC: 63 AN: 60024

GnomAD4 genome AF: 0.00539 AC: 812 AN: 150630 Hom.: 3 Cov.: 30 AF XY: 0.00539 AC XY: 396 AN XY: 73502

African (AFR) AF: 0.0189 AC: 773 AN: 40982

American (AMR) AF: 0.00173 AC: 26 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5102

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67686

Other (OTH) AF: 0.00381 AC: 8 AN: 2098

Alfa AF: 0.00769 Hom.: 4

Bravo AF: 0.00617

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.0
DANN	Benign	0.80
PhyloP100		-3.5
Mutation Taster		=100/0	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

dbSNP: rs140019547; hg19: chr1-160124942; COSMIC: COSV63628801;