NM_014164.6:c.527_528delGTinsAC

Variant names:

• chr19-35169605-GT-AC
• NM_014164.6:c.527_528delGTinsAC
• FXYD5 p.Arg176His

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014164.6(FXYD5):​c.527_528delGTinsAC​(p.Arg176His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R176L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FXYD5 NM_014164.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD5	NM_014164.6	MANE Select	c.527_528delGTinsAC	p.Arg176His	missense	N/A	NP_054883.3
	FXYD5	NM_001164605.2		c.527_528delGTinsAC	p.Arg176His	missense	N/A	NP_001158077.1	Q96DB9-1
	FXYD5	NM_144779.3		c.527_528delGTinsAC	p.Arg176His	missense	N/A	NP_659003.1	Q96DB9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD5	ENST00000392219.7	TSL:1 MANE Select	c.527_528delGTinsAC	p.Arg176His	missense	N/A	ENSP00000376053.2	Q96DB9-1
	FXYD5	ENST00000342879.7	TSL:1	c.527_528delGTinsAC	p.Arg176His	missense	N/A	ENSP00000344254.3	Q96DB9-1
	FXYD5	ENST00000392217.3	TSL:1	c.314_315delGTinsAC	p.Arg105His	missense	N/A	ENSP00000376051.3	Q96DB9-2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-35660508;