11-117842472-C-T

Position:

• chr11-117842472-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.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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXYD6	NM_022003.4	c.58+247G>A		intron_variant		ENST00000526014.6	NP_071286.1
FXYD6-FXYD2	NM_001243598.4	c.58+247G>A		intron_variant			NP_001230527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXYD6	ENST00000526014.6	c.58+247G>A		intron_variant		1	NM_022003.4	ENSP00000433312	P1

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

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0237

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0556

Gnomad4 OTH AF: 0.0417

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.80
DANN	Benign	0.56

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: rs12363888; hg19: chr11-117713187;