11-117867032-C-A

Variant names:

• chr11-117867032-C-A
• rs876797
• NM_022003.4:c.-6+9560G>T

Variant summary

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

The NM_022003.4(FXYD6):​c.-6+9560G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,142 control chromosomes in the GnomAD database, including 4,162 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 0.21 (4162 hom., cov: 32)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022003.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6	NM_022003.4	MANE Select	c.-6+9560G>T		intron	N/A	NP_071286.1
	FXYD6-FXYD2	NM_001204268.3		c.-6+9560G>T		intron	N/A	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.-6+9560G>T		intron	N/A	NP_001230527.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6	ENST00000526014.6	TSL:1 MANE Select	c.-6+9560G>T		intron	N/A	ENSP00000433312.1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.-6+9560G>T		intron	N/A	ENSP00000482442.1
	FXYD6	ENST00000260282.8	TSL:1	c.-178-8746G>T		intron	N/A	ENSP00000260282.4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31928 AN: 152024 Hom.: 4161 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.210 AC: 31927 AN: 152142 Hom.: 4162 Cov.: 32 AF XY: 0.218 AC XY: 16182 AN XY: 74366

African (AFR) AF: 0.0775 AC: 3219 AN: 41534

American (AMR) AF: 0.332 AC: 5065 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3466

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1422 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3620 AN: 10568

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15437 AN: 67994

Other (OTH) AF: 0.213 AC: 448 AN: 2108

Alfa AF: 0.222 Hom.: 17405

Bravo AF: 0.207

Asia WGS AF: 0.264 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.83
DANN	Benign	0.77
PhyloP100		-0.32
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: rs876797; hg19: chr11-117737747;