chr11-117859115-G-A

Position:

• chr11-117859115-G-A

Variant summary

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

The NM_022003.4(FXYD6):​c.-5-16334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 109,922 control chromosomes in the GnomAD database, including 7,556 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 0.38 (7556 hom., cov: 27)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.852

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXYD6	NM_022003.4	c.-5-16334C>T		intron_variant		ENST00000526014.6	NP_071286.1
FXYD6-FXYD2	NM_001243598.4	c.-5-16334C>T		intron_variant			NP_001230527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXYD6	ENST00000526014.6	c.-5-16334C>T		intron_variant		1	NM_022003.4	ENSP00000433312	P1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 41440 AN: 109796 Hom.: 7524 Cov.: 27

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.378 AC: 41519 AN: 109922 Hom.: 7556 Cov.: 27 AF XY: 0.379 AC XY: 20133 AN XY: 53100

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.343

Alfa AF: 0.227 Hom.: 724

Bravo AF: 0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.80

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: rs7121573; hg19: chr11-117729830;