11-117839039-C-T

Position:

• chr11-117839039-C-T

Variant summary

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

The NM_022003.4(FXYD6):​c.*21+742G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 152,674 control chromosomes in the GnomAD database, including 36,366 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 0.68 (36191 hom., cov: 32)
  • Exomes 𝑓: 0.75 (175 hom.)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.97

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:39978): (FXYD6-FXYD2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FXYD domain-containing ion transport regulator 6 (GeneID 53826) and sodium/potassium-transporting ATPase subunit gamma (GeneID 486) genes on chromosome 11. One read-through transcript produces a fusion protein that shares sequence identity with each individual gene product, while another read-through transcript encodes a protein that has a distinct C-terminus and only shares sequence identity with the upstream locus (GeneID 53826). [provided by RefSeq, Aug 2011]

FXYD6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXYD6	NM_022003.4	c.*21+742G>A		intron_variant		ENST00000526014.6	NP_071286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXYD6	ENST00000526014.6	c.*21+742G>A		intron_variant		1	NM_022003.4	ENSP00000433312.1
FXYD6-FXYD2	ENST00000614497.5	c.259+742G>A		intron_variant		3		ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102830 AN: 151944 Hom.: 36194 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.755 AC: 462 AN: 612 Hom.: 175 Cov.: 0 AF XY: 0.739 AC XY: 257 AN XY: 348

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.670

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.429

Gnomad4 FIN exome AF: 0.643

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.676 AC: 102859 AN: 152062 Hom.: 36191 Cov.: 32 AF XY: 0.681 AC XY: 50584 AN XY: 74322

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.763

Gnomad4 OTH AF: 0.637

Alfa AF: 0.744 Hom.: 46971

Bravo AF: 0.662

Asia WGS AF: 0.665 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.64

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: rs564989; hg19: chr11-117709754;