rs140956604

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_014164.6(FXYD5):c.134G>A(p.Arg45Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,529,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

FXYD5
NM_014164.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0930

Publications

5 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066459477).

BP6

Variant 19-35157493-G-A is Benign according to our data. Variant chr19-35157493-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2341034.Status of the report is criteria_provided_single_submitter, 1 stars.

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	UniProt
FXYD5	NM_014164.6	MANE Select	c.134G>A	p.Arg45Gln	missense	Exon 3 of 9	NP_054883.3
FXYD5	NM_001320912.2		c.134G>A	p.Arg45Gln	missense	Exon 3 of 9	NP_001307841.1	F5H4X8
FXYD5	NM_001164605.2		c.134G>A	p.Arg45Gln	missense	Exon 3 of 9	NP_001158077.1	Q96DB9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FXYD5	ENST00000392219.7	TSL:1 MANE Select	c.134G>A	p.Arg45Gln	missense	Exon 3 of 9	ENSP00000376053.2	Q96DB9-1
FXYD5	ENST00000342879.7	TSL:1	c.134G>A	p.Arg45Gln	missense	Exon 2 of 8	ENSP00000344254.3	Q96DB9-1
FXYD5	ENST00000718431.1		c.134G>A	p.Arg45Gln	missense	Exon 3 of 10	ENSP00000520816.1	A0ABB0MVH5

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000159

AC:

AN:

251068

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000110

AC:

151

AN:

1377664

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

690062

show subpopulations

African (AFR)

AF:

0.000598

AC:

AN:

31748

American (AMR)

AF:

0.000157

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25570

East Asian (EAS)

AF:

0.000565

AC:

AN:

38970

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.0000927

AC:

AN:

1035944

Other (OTH)

AF:

0.0000869

AC:

AN:

57546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000204

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000458

AC:

AN:

41528

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000951

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.77

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.58

M_CAP

Benign

0.016

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.90

PhyloP100

-0.093

PrimateAI

Benign

0.22

PROVEAN

Benign

1.1

REVEL

Benign

0.019

Sift

Benign

0.54

Sift4G

Benign

0.43

Polyphen

0.0010

Vest4

0.074

MVP

0.35

MPC

0.14

ClinPred

0.0026

GERP RS

-2.1

Varity_R

0.013

gMVP

0.046

Mutation Taster

=99/1

polymorphism

(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