Variant X-120366532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001142447.3(ATP1B4):c.71C>T(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000407 in 1,203,155 control chromosomes in the GnomAD database, including 1 homozygotes. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000028 ( 0 hom. 8 hem. )

Consequence

ATP1B4
NM_001142447.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055837482).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ATP1B4	NM_001142447.3 linkuse as main transcript	c.71C>T	p.Pro24Leu	missense_variant	2/8	ENST00000218008.8
ATP1B4	NM_012069.5 linkuse as main transcript	c.71C>T	p.Pro24Leu	missense_variant	2/8
ATP1B4	XM_017029381.2 linkuse as main transcript	c.71C>T	p.Pro24Leu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP1B4	ENST00000218008.8 linkuse as main transcript	c.71C>T	p.Pro24Leu	missense_variant	2/8	1	NM_001142447.3	P1	Q9UN42-1
ATP1B4	ENST00000361319.3 linkuse as main transcript	c.71C>T	p.Pro24Leu	missense_variant	2/8	1			Q9UN42-2
ATP1B4	ENST00000539306.5 linkuse as main transcript	c.71C>T	p.Pro24Leu	missense_variant	2/7	2

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

109668

Hom.:

Cov.:

AF XY:

0.0000623

AC XY:

AN XY:

32100

show subpopulations

Gnomad AFR

AF:

0.000533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000391

AC:

AN:

179054

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

65256

show subpopulations

Gnomad AFR exome

AF:

0.000229

Gnomad AMR exome

AF:

0.0000368

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000284

AC:

AN:

1093437

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

359587

show subpopulations

Gnomad4 AFR exome

AF:

0.000305

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000179

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000164

AC:

AN:

109718

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

32160

show subpopulations

Gnomad4 AFR

AF:

0.000598

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000412

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 16, 2023

The c.71C>T (p.P24L) alteration is located in exon 2 (coding exon 2) of the ATP1B4 gene. This alteration results from a C to T substitution at nucleotide position 71, causing the proline (P) at amino acid position 24 to be replaced by a leucine (L). 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

Benign

0.096

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0082

T;T;.

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N

MutationTaster

Benign

0.79

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.057

Sift

Benign

0.17

T;T;T

Sift4G

Uncertain

0.055

T;D;T

Polyphen

0.024

B;B;B

Vest4

0.22

MVP

0.65

MPC

0.17

ClinPred

0.043

GERP RS

4.3

Varity_R

0.071

gMVP

0.29

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