rs3168238

Variant names:

• chr11-117838930-T-G
• rs3168238
• NM_022003.4:c.*22-653A>C

Variant summary

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

The NM_001204268.3(FXYD6-FXYD2):​c.259+851A>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-FXYD2 NM_001204268.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 2 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]

FXYD6-AS1 (HGNC:56067): (FXYD6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204268.3. 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.*22-653A>C		intron	N/A	NP_071286.1
	FXYD6-FXYD2	NM_001204268.3		c.259+851A>C		intron	N/A	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.272+851A>C		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.*22-653A>C		intron	N/A	ENSP00000433312.1
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.259+851A>C		intron	N/A	ENSP00000482442.1
	FXYD6	ENST00000260282.8	TSL:1	c.*22-653A>C		intron	N/A	ENSP00000260282.4

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

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.0195 AC: 10 AN: 512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 40

South Asian (SAS) AF: 0.0227 AC: 3 AN: 132

European-Finnish (FIN) AF: 0.0833 AC: 1 AN: 12

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0785 AC: 111 AN: 1414

Other (OTH) AF: 0.0278 AC: 2 AN: 72

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

African (AFR) AF: 0.0108 AC: 451 AN: 41586

American (AMR) AF: 0.0236 AC: 361 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00538 AC: 26 AN: 4830

European-Finnish (FIN) AF: 0.0834 AC: 884 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0597 AC: 4062 AN: 68022

Other (OTH) AF: 0.0370 AC: 78 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.77
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3168238; hg19: chr11-117709645;