Variant rs2285515 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.488-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,571,758 control chromosomes in the GnomAD database, including 107,191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9612 hom., cov: 31)

Exomes 𝑓: 0.36 ( 97579 hom. )

Consequence

FXYD5
NM_014164.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

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 (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD5	NM_014164.6 linkuse as main transcript	c.488-19T>C		intron_variant		ENST00000392219.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD5	ENST00000392219.7 linkuse as main transcript	c.488-19T>C		intron_variant		1	NM_014164.6	P2	Q96DB9-1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53016

AN:

151836

Hom.:

9609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.310

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.328

GnomAD3 exomes

AF:

0.332

AC:

82657

AN:

248684

Hom.:

14603

AF XY:

0.337

AC XY:

45310

AN XY:

134600

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.131

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.334

GnomAD4 exome

AF:

0.364

AC:

516811

AN:

1419804

Hom.:

97579

Cov.:

AF XY:

0.364

AC XY:

257600

AN XY:

708580

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.260

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.327

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.384

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.349

AC:

53036

AN:

151954

Hom.:

9612

Cov.:

AF XY:

0.346

AC XY:

25718

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.281

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.397

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.369

Hom.:

13935

Bravo

AF:

0.341

Asia WGS

AF:

0.204

AC:

710

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

DANN

Benign

0.60

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