17-7654101-A-T

Variant names:

• chr17-7654101-A-T
• rs1642763
• NM_001678.5:c.396A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001678.5(ATP1B2):​c.396A>T​(p.Gly132Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: ATP1B2 NM_001678.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 44 publications found

Genes affected

ATP1B2 (HGNC:805): (ATPase Na+/K+ transporting subunit beta 2) The protein encoded by this gene belongs to the family of Na+/K+ and H+/K+ ATPases beta chain proteins, 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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. The glycoprotein subunit of Na+/K+ -ATPase is encoded by multiple genes. This gene encodes a beta 2 subunit. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.339 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001678.5. 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
	ATP1B2	NM_001678.5	MANE Select	c.396A>T	p.Gly132Gly	synonymous	Exon 4 of 7	NP_001669.3
	ATP1B2	NM_001303263.2		c.150A>T	p.Gly50Gly	synonymous	Exon 3 of 6	NP_001290192.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B2	ENST00000250111.9	TSL:1 MANE Select	c.396A>T	p.Gly132Gly	synonymous	Exon 4 of 7	ENSP00000250111.4	P14415
	ATP1B2	ENST00000937622.1		c.267A>T	p.Gly89Gly	synonymous	Exon 3 of 6	ENSP00000607681.1
	ATP1B2	ENST00000896722.1		c.396A>T	p.Gly132Gly	synonymous	Exon 4 of 8	ENSP00000566781.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		-0.34
PromoterAI		-0.0084	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1642763; hg19: chr17-7557419;