Variant X-120375382-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001142447.3(ATP1B4):c.573C>G(p.Asp191Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,205,442 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000040 ( 0 hom. 18 hem. )

Consequence

ATP1B4
NM_001142447.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

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]

ATP1B4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATP1B4	NM_001142447.3 linkuse as main transcript	c.573C>G	p.Asp191Glu	missense_variant	5/8	ENST00000218008.8
ATP1B4	NM_012069.5 linkuse as main transcript	c.561C>G	p.Asp187Glu	missense_variant	5/8
ATP1B4	XM_017029381.2 linkuse as main transcript	c.573C>G	p.Asp191Glu	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B4	ENST00000218008.8 linkuse as main transcript	c.573C>G	p.Asp191Glu	missense_variant	5/8	1	NM_001142447.3	P1	Q9UN42-1
ATP1B4	ENST00000361319.3 linkuse as main transcript	c.561C>G	p.Asp187Glu	missense_variant	5/8	1			Q9UN42-2
ATP1B4	ENST00000539306.5 linkuse as main transcript	c.444C>G	p.Asp148Glu	missense_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000541

AC:

AN:

111000

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33188

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000384

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000378

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000451

AC:

AN:

177538

Hom.:

AF XY:

0.0000321

AC XY:

AN XY:

62334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000377

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000402

AC:

AN:

1094442

Hom.:

Cov.:

AF XY:

0.0000500

AC XY:

AN XY:

360054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000172

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000541

AC:

AN:

111000

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33188

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000384

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.573C>G (p.D191E) alteration is located in exon 5 (coding exon 5) of the ATP1B4 gene. This alteration results from a C to G substitution at nucleotide position 573, causing the aspartic acid (D) at amino acid position 191 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.025

D;D;T

Sift4G

Uncertain

0.043

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.69

MutPred

0.50

.;Gain of disorder (P = 0.1101);.;

MVP

0.54

MPC

0.65

ClinPred

0.49

GERP RS

5.6

Varity_R

0.59

gMVP

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over