X-120366604-T-A

Variant names:

• chrX-120366604-T-A
• rs2072452
• NM_001142447.3:c.143T>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/21 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. V48G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ATP1B4 NM_001142447.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 7 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142447.3. 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
	ATP1B4	NM_001142447.3	MANE Select	c.143T>A	p.Val48Glu	missense	Exon 2 of 8	NP_001135919.1
	ATP1B4	NM_012069.5		c.143T>A	p.Val48Glu	missense	Exon 2 of 8	NP_036201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP1B4	ENST00000218008.8	TSL:1 MANE Select	c.143T>A	p.Val48Glu	missense	Exon 2 of 8	ENSP00000218008.3
	ATP1B4	ENST00000361319.3	TSL:1	c.143T>A	p.Val48Glu	missense	Exon 2 of 8	ENSP00000355346.3
	ATP1B4	ENST00000955253.1		c.143T>A	p.Val48Glu	missense	Exon 2 of 7	ENSP00000625312.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.23
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.020
Sift	Benign	0.086	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.18		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
Mutation Taster		=95/5	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: rs2072452; hg19: chrX-119500459;