11-117839039-C-T

Variant names:

• chr11-117839039-C-T
• rs564989
• ENST00000527429.5:n.1596G>A

Variant summary

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

The ENST00000527429.5(FXYD6):​n.1596G>A variant causes a non coding transcript exon 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 ENST00000527429.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.97
• Publications: 5 publications found

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-AS1 (HGNC:56067): (FXYD6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FXYD6	NM_022003.4	c.*21+742G>A		intron_variant	Intron 7 of 7	ENST00000526014.6	NP_071286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD6	ENST00000526014.6	c.*21+742G>A		intron_variant	Intron 7 of 7	1	NM_022003.4	ENSP00000433312.1
FXYD6-FXYD2	ENST00000614497.5	c.259+742G>A		intron_variant	Intron 6 of 10	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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.670 AC: 71 AN: 106

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 0.429 AC: 6 AN: 14

European-Finnish (FIN) AF: 0.643 AC: 9 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.787 AC: 359 AN: 456

Other (OTH) AF: 0.813 AC: 13 AN: 16

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

African (AFR) AF: 0.464 AC: 19236 AN: 41434

American (AMR) AF: 0.739 AC: 11291 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2405 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3606 AN: 5166

South Asian (SAS) AF: 0.690 AC: 3326 AN: 4820

European-Finnish (FIN) AF: 0.836 AC: 8851 AN: 10590

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51901 AN: 67982

Other (OTH) AF: 0.637 AC: 1343 AN: 2108

Alfa AF: 0.716 Hom.: 64562

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
PhyloP100		-5.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs564989; hg19: chr11-117709754;