rs12363888

Variant names:

• chr11-117842472-C-T
• rs12363888
• NM_022003.4:c.58+247G>A

Variant summary

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

The NM_022003.4(FXYD6):​c.58+247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 152,242 control chromosomes in the GnomAD database, including 136 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 0.036 (136 hom., cov: 32)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 0 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0541 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.58+247G>A		intron	N/A	NP_071286.1
	FXYD6-FXYD2	NM_001204268.3		c.58+247G>A		intron	N/A	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.58+247G>A		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.58+247G>A		intron	N/A	ENSP00000433312.1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.58+247G>A		intron	N/A	ENSP00000482442.1
	FXYD6	ENST00000260282.8	TSL:1	c.58+247G>A		intron	N/A	ENSP00000260282.4

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5516 AN: 152124 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0362 AC: 5515 AN: 152242 Hom.: 136 Cov.: 32 AF XY: 0.0344 AC XY: 2558 AN XY: 74430

African (AFR) AF: 0.0103 AC: 428 AN: 41544

American (AMR) AF: 0.0274 AC: 419 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0237 AC: 114 AN: 4818

European-Finnish (FIN) AF: 0.0387 AC: 410 AN: 10608

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0556 AC: 3781 AN: 68010

Other (OTH) AF: 0.0417 AC: 88 AN: 2110

Alfa AF: 0.0481 Hom.: 26

Bravo AF: 0.0333

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.80
DANN	Benign	0.56
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs12363888; hg19: chr11-117713187;