rs512481

Positions:

• chr11-117848165-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022003.4(FXYD6):​c.-5-5384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,900 control chromosomes in the GnomAD database, including 12,272 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 0.39 (12272 hom., cov: 32)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

Genes affected

FXYD6 (HGNC:4030): (FXYD domain containing ion transport regulator 6) This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes phosphohippolin, which likely affects the activity of Na,K-ATPase. Multiple alternatively spliced transcript variants encoding the same protein have been described. Related pseudogenes have been identified on chromosomes 10 and X. Read-through transcripts have been observed between this locus and the downstream sodium/potassium-transporting ATPase subunit gamma (FXYD2, GeneID 486) locus.[provided by RefSeq, Feb 2011]

FXYD6-FXYD2 (HGNC:):

ACMG classification

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 = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD6	NM_022003.4	c.-5-5384C>T		intron_variant		ENST00000526014.6
FXYD6-FXYD2	NM_001243598.4	c.-5-5384C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD6	ENST00000526014.6	c.-5-5384C>T		intron_variant		1	NM_022003.4	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59601 AN: 151782 Hom.: 12272 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.392 AC: 59613 AN: 151900 Hom.: 12272 Cov.: 32 AF XY: 0.388 AC XY: 28799 AN XY: 74254

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.392

Alfa AF: 0.456 Hom.: 32629

Bravo AF: 0.381

Asia WGS AF: 0.355 AC: 1233 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	1.3
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs512481; hg19: chr11-117718880;