Variant rs12110 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014164.6(FXYD5):c.527G>A(p.Arg176His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,606,312 control chromosomes in the GnomAD database, including 523,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.83 ( 53468 hom., cov: 31)

Exomes 𝑓: 0.80 ( 470210 hom. )

Consequence

FXYD5
NM_014164.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

FXYD5 (HGNC:4029): (FXYD domain containing ion transport regulator 5) This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. Mouse FXYD5 has been termed RIC (Related to Ion Channel). FXYD2, also known as the gamma subunit of the Na,K-ATPase, regulates the properties of that enzyme. FXYD1 (phospholemman), FXYD2 (gamma), FXYD3 (MAT-8), FXYD4 (CHIF), and FXYD5 (RIC) have been shown to induce channel activity in experimental expression systems. Transmembrane topology has been established for two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. This gene product, FXYD5, is a glycoprotein that functions in the up-regulation of chemokine production, and it is involved in the reduction of cell adhesion via its ability to down-regulate E-cadherin. It also promotes metastasis, and has been linked to a variety of cancers. Alternative splicing results in multiple transcript variants. [RefSeq curation by Kathleen J. Sweadner, Ph.D., sweadner@helix.mgh.harvard.edu., Sep 2009]

FXYD5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0205597E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD5	NM_014164.6 link	c.527G>A	p.Arg176His	missense_variant	Exon 9 of 9	ENST00000392219.7	NP_054883.3	Q96DB9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD5	ENST00000392219.7 link	c.527G>A	p.Arg176His	missense_variant	Exon 9 of 9	1	NM_014164.6	ENSP00000376053.2		Q96DB9-1

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126916

AN:

152054

Hom.:

53411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.948

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.841

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.799

GnomAD3 exomes

AF:

0.812

AC:

202037

AN:

248846

Hom.:

82628

AF XY:

0.808

AC XY:

108779

AN XY:

134704

show subpopulations

Gnomad AFR exome

AF:

0.953

Gnomad AMR exome

AF:

0.892

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.776

Gnomad SAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.762

Gnomad NFE exome

AF:

0.779

Gnomad OTH exome

AF:

0.790

GnomAD4 exome

AF:

0.803

AC:

1166949

AN:

1454140

Hom.:

470210

Cov.:

AF XY:

0.802

AC XY:

580811

AN XY:

723890

show subpopulations

Gnomad4 AFR exome

AF:

0.951

Gnomad4 AMR exome

AF:

0.886

Gnomad4 ASJ exome

AF:

0.677

Gnomad4 EAS exome

AF:

0.802

Gnomad4 SAS exome

AF:

0.869

Gnomad4 FIN exome

AF:

0.760

Gnomad4 NFE exome

AF:

0.795

Gnomad4 OTH exome

AF:

0.800

GnomAD4 genome

AF:

0.835

AC:

127032

AN:

152172

Hom.:

53468

Cov.:

AF XY:

0.832

AC XY:

61894

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.948

Gnomad4 AMR

AF:

0.841

Gnomad4 ASJ

AF:

0.678

Gnomad4 EAS

AF:

0.795

Gnomad4 SAS

AF:

0.872

Gnomad4 FIN

AF:

0.759

Gnomad4 NFE

AF:

0.787

Gnomad4 OTH

AF:

0.797

Alfa

AF:

0.788

Hom.:

121660

Bravo

AF:

0.845

TwinsUK

AF:

0.803

AC:

2978

ALSPAC

AF:

0.809

AC:

3117

ESP6500AA

AF:

0.946

AC:

4167

ESP6500EA

AF:

0.778

AC:

6690

ExAC

AF:

0.811

AC:

98497

Asia WGS

AF:

0.865

AC:

3012

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.9

DANN

Benign

0.58

DEOGEN2

Benign

0.0076

T;T;T;T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.42

.;.;.;.;T;T

MetaRNN

Benign

0.0000010

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.85

L;L;L;L;L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.48

N;N;.;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.64

T;T;.;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;B;B

Vest4

0.014

MPC

0.15

ClinPred

0.0024

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.012

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over