ENST00000718431.1:c.*186A>C

Variant names:

• chr19-35171906-A-C
• rs739495
• ENST00000718431.1:c.*186A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000718431.1(FXYD5):​c.*186A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 149,566 control chromosomes in the GnomAD database, including 7,006 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 0.26 (7006 hom., cov: 31)
• Consequence: FXYD5 ENST00000718431.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 7 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD5	ENST00000718431.1	c.*186A>C		downstream_gene_variant				ENSP00000520816.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 38364 AN: 149450 Hom.: 6994 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.271

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 38412 AN: 149566 Hom.: 7006 Cov.: 31 AF XY: 0.259 AC XY: 18930 AN XY: 72964

African (AFR) AF: 0.129 AC: 5316 AN: 41232

American (AMR) AF: 0.390 AC: 5844 AN: 14980

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1110 AN: 3434

East Asian (EAS) AF: 0.225 AC: 1019 AN: 4530

South Asian (SAS) AF: 0.430 AC: 2033 AN: 4726

European-Finnish (FIN) AF: 0.269 AC: 2784 AN: 10354

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.288 AC: 19299 AN: 67044

Other (OTH) AF: 0.275 AC: 570 AN: 2072

Alfa AF: 0.290 Hom.: 2691

Asia WGS AF: 0.394 AC: 1322 AN: 3358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.96
DANN	Benign	0.48
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs739495; hg19: chr19-35662809;