Variant X-120379539-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001142447.3(ATP1B4):c.979G>C(p.Val327Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000414 in 1,209,142 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

ATP1B4
NM_001142447.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24462926).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP1B4	NM_001142447.3 linkuse as main transcript	c.979G>C	p.Val327Leu	missense_variant	8/8	ENST00000218008.8	NP_001135919.1
ATP1B4	NM_012069.5 linkuse as main transcript	c.967G>C	p.Val323Leu	missense_variant	8/8		NP_036201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP1B4	ENST00000218008.8 linkuse as main transcript	c.979G>C	p.Val327Leu	missense_variant	8/8	1	NM_001142447.3	ENSP00000218008	P1	Q9UN42-1
ATP1B4	ENST00000361319.3 linkuse as main transcript	c.967G>C	p.Val323Leu	missense_variant	8/8	1		ENSP00000355346		Q9UN42-2
ATP1B4	ENST00000539306.5 linkuse as main transcript	c.850G>C	p.Val284Leu	missense_variant	7/7	2		ENSP00000443334

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112057

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34213

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

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:

0.0000275

AC:

AN:

181942

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

66534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000364

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:

0.00000365

AC:

AN:

1097085

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362469

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112057

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34213

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

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

Feb 07, 2023

The c.979G>C (p.V327L) alteration is located in exon 8 (coding exon 8) of the ATP1B4 gene. This alteration results from a G to C substitution at nucleotide position 979, causing the valine (V) at amino acid position 327 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;T;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

D;D;D

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.065

T;D;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.17

B;B;B

Vest4

0.40

MutPred

0.66

.;Loss of catalytic residue at V327 (P = 0.0572);.;

MVP

0.75

MPC

0.31

ClinPred

0.17

GERP RS

4.4

Varity_R

0.30

gMVP

0.95

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