rs2072452

Positions:

• chrX-120366604-T-A
• chrX-120366604-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142447.3(ATP1B4):​c.143T>A​(p.Val48Glu) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V48A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ATP1B4 NM_001142447.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

Genes affected

ATP1B4 (HGNC:808): (ATPase Na+/K+ transporting family member beta 4) This gene has been found in all vertebrate genomes sequenced to date. However, this gene has undergone a change in function in placental mammals compared to other species. Specifically, in fish, avian, and amphibian species, this gene encodes plasma membrane-bound beta-subunits of Na,K-ATPase. In placental mammals, the encoded protein interacts with the nuclear transcriptional coregulator SKIP and may be involved in the regulation of TGF-beta signaling. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095897496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B4	NM_001142447.3	c.143T>A	p.Val48Glu	missense_variant	2/8	ENST00000218008.8	NP_001135919.1
ATP1B4	NM_012069.5	c.143T>A	p.Val48Glu	missense_variant	2/8		NP_036201.1
ATP1B4	XM_017029381.2	c.143T>A	p.Val48Glu	missense_variant	2/5		XP_016884870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B4	ENST00000218008.8	c.143T>A	p.Val48Glu	missense_variant	2/8	1	NM_001142447.3	ENSP00000218008.3
ATP1B4	ENST00000361319.3	c.143T>A	p.Val48Glu	missense_variant	2/8	1		ENSP00000355346.3
ATP1B4	ENST00000539306.5	c.143T>A	p.Val48Glu	missense_variant	2/7	2		ENSP00000443334.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.33
DEOGEN2	Benign	0.0063	T;T;.
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.040	N;N;N
REVEL	Benign	0.020
Sift	Benign	0.086	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.27
MutPred		0.18		Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.37
MPC		0.34
ClinPred		0.068	T
GERP RS		-2.0
Varity_R		0.17
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs2072452; hg19: chrX-119500459;