11-117838930-T-G

Position:

• chr11-117838930-T-G

Variant summary

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

The NM_022003.4(FXYD6):​c.*22-653A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 154,504 control chromosomes in the GnomAD database, including 184 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 0.039 (178 hom., cov: 32)
  • Exomes 𝑓: 0.058 (6 hom.)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXYD6	NM_022003.4	c.*22-653A>C		intron_variant		ENST00000526014.6	NP_071286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXYD6	ENST00000526014.6	c.*22-653A>C		intron_variant		1	NM_022003.4	ENSP00000433312.1
FXYD6-FXYD2	ENST00000614497.5	c.259+851A>C		intron_variant		3		ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5966 AN: 152192 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0834

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0374

GnomAD4 exome AF: 0.0579 AC: 127 AN: 2194 Hom.: 6 Cov.: 0 AF XY: 0.0621 AC XY: 71 AN XY: 1144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0785

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0392 AC: 5966 AN: 152310 Hom.: 178 Cov.: 32 AF XY: 0.0383 AC XY: 2856 AN XY: 74482

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.0236

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.0834

Gnomad4 NFE AF: 0.0597

Gnomad4 OTH AF: 0.0370

Alfa AF: 0.0490 Hom.: 25

Bravo AF: 0.0336

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3168238; hg19: chr11-117709645;