ENST00000614497.5:c.260-3312C>T

Variant names:

• chr11-117826029-G-A
• rs678776
• ENST00000614497.5:c.260-3312C>T

Variant summary

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

The ENST00000614497.5(FXYD6-FXYD2):​c.260-3312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,116 control chromosomes in the GnomAD database, including 4,749 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 0.24 (4749 hom., cov: 32)
• Consequence: FXYD6-FXYD2 ENST00000614497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 4 publications found

Genes affected

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]

FXYD2 (HGNC:4026): (FXYD domain containing ion transport regulator 2) This gene encodes a member of the FXYD family of transmembrane proteins. This particular protein encodes the sodium/potassium-transporting ATPase subunit gamma. Mutations in this gene have been associated with Renal Hypomagnesemia-2. Alternatively spliced transcript variants have been described. Read-through transcripts have been observed between this locus and the upstream FXYD domain-containing ion transport regulator 6 (FXYD6, GeneID 53826) locus.[provided by RefSeq, Feb 2011]

FXYD2 Gene-Disease associations (from GenCC):

• renal hypomagnesemia 2

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000614497.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6-FXYD2	NM_001204268.3		c.260-3312C>T		intron	N/A	NP_001191197.1	A0A087WZ82
	FXYD6-FXYD2	NM_001243598.4		c.273-3312C>T		intron	N/A	NP_001230527.1	A0A0A6YYL5
	FXYD2	NM_021603.4		c.19+1966C>T		intron	N/A	NP_067614.1	P54710-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.260-3312C>T		intron	N/A	ENSP00000482442.1	A0A087WZ82
	FXYD2	ENST00000260287.2	TSL:1	c.19+1966C>T		intron	N/A	ENSP00000260287.2	P54710-2
	FXYD6-FXYD2	ENST00000532984.1	TSL:3	c.273-3312C>T		intron	N/A	ENSP00000463024.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35943 AN: 151996 Hom.: 4745 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.236 AC: 35954 AN: 152116 Hom.: 4749 Cov.: 32 AF XY: 0.235 AC XY: 17505 AN XY: 74384

African (AFR) AF: 0.122 AC: 5081 AN: 41494

American (AMR) AF: 0.211 AC: 3224 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1323 AN: 5170

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2532 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19881 AN: 67988

Other (OTH) AF: 0.264 AC: 556 AN: 2108

Alfa AF: 0.281 Hom.: 3831

Bravo AF: 0.228

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.43
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs678776;

hg19: chr11-117696744;