19-35157462-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014164.6(FXYD5):c.103T>G(p.Ser35Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,587,782 control chromosomes in the GnomAD database, including 70,309 homozygotes. 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.

Frequency

Genomes: 𝑓 0.30 ( 7771 hom., cov: 31)

Exomes 𝑓: 0.28 ( 62538 hom. )

Consequence

FXYD5
NM_014164.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.28

Publications

35 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0512871E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014164.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FXYD5	NM_014164.6	MANE Select	c.103T>G	p.Ser35Ala	missense	Exon 3 of 9	NP_054883.3
FXYD5	NM_001320912.2		c.103T>G	p.Ser35Ala	missense	Exon 3 of 9	NP_001307841.1
FXYD5	NM_001164605.2		c.103T>G	p.Ser35Ala	missense	Exon 3 of 9	NP_001158077.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FXYD5	ENST00000392219.7	TSL:1 MANE Select	c.103T>G	p.Ser35Ala	missense	Exon 3 of 9	ENSP00000376053.2
FXYD5	ENST00000342879.7	TSL:1	c.103T>G	p.Ser35Ala	missense	Exon 2 of 8	ENSP00000344254.3
FXYD5	ENST00000718431.1		c.103T>G	p.Ser35Ala	missense	Exon 3 of 10	ENSP00000520816.1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45770

AN:

151778

Hom.:

7764

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.261

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.326

AC:

81737

AN:

250832

AF XY:

0.319

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.823

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.276

AC:

396315

AN:

1435884

Hom.:

62538

Cov.:

AF XY:

0.276

AC XY:

197638

AN XY:

715904

show subpopulations

African (AFR)

AF:

0.314

AC:

10322

AN:

32848

American (AMR)

AF:

0.365

AC:

16291

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5943

AN:

25956

East Asian (EAS)

AF:

0.824

AC:

32477

AN:

39396

South Asian (SAS)

AF:

0.304

AC:

26058

AN:

85664

European-Finnish (FIN)

AF:

0.308

AC:

16436

AN:

53282

Middle Eastern (MID)

AF:

0.258

AC:

1476

AN:

5714

European-Non Finnish (NFE)

AF:

0.248

AC:

269651

AN:

1088822

Other (OTH)

AF:

0.296

AC:

17661

AN:

59606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

11123

22247

33370

44494

55617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9354

18708

28062

37416

46770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.302

AC:

45819

AN:

151898

Hom.:

7771

Cov.:

AF XY:

0.308

AC XY:

22866

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.322

AC:

13336

AN:

41368

American (AMR)

AF:

0.313

AC:

4778

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

788

AN:

3468

East Asian (EAS)

AF:

0.808

AC:

4158

AN:

5144

South Asian (SAS)

AF:

0.315

AC:

1512

AN:

4806

European-Finnish (FIN)

AF:

0.311

AC:

3278

AN:

10556

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17185

AN:

67954

Other (OTH)

AF:

0.291

AC:

613

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1561

3122

4683

6244

7805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.274

Hom.:

27836

Bravo

AF:

0.308

TwinsUK

AF:

0.248

AC:

921

ALSPAC

AF:

0.254

AC:

979

ESP6500AA

AF:

0.325

AC:

1434

ESP6500EA

AF:

0.252

AC:

2165

ExAC

AF:

0.321

AC:

38947

Asia WGS

AF:

0.538

AC:

1869

AN:

3478

EpiCase

AF:

0.247

EpiControl

AF:

0.245

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.030

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0000010

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.20

PhyloP100

-2.3

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.82

REVEL

Benign

0.041

Sift

Benign

0.16

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.073

MPC

0.096

ClinPred

0.0055

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.035

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over