11-117839823-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001204268.3(FXYD6-FXYD2):​c.217G>A​(p.Ala73Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FXYD6-FXYD2
NM_001204268.3 missense

Scores

11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05
Variant links:
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07854885).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FXYD6NM_022003.4 linkc.267G>A p.Glu89Glu synonymous_variant Exon 7 of 8 ENST00000526014.6 NP_071286.1 Q9H0Q3-1A0A024R3J8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FXYD6-FXYD2ENST00000614497.5 linkc.217G>A p.Ala73Thr missense_variant Exon 6 of 11 3 ENSP00000482442.1 A0A087WZ82
FXYD6ENST00000526014.6 linkc.267G>A p.Glu89Glu synonymous_variant Exon 7 of 8 1 NM_022003.4 ENSP00000433312.1 Q9H0Q3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 27, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.217G>A (p.A73T) alteration is located in exon 6 (coding exon 5) of the FXYD6-FXYD2 gene. This alteration results from a G to A substitution at nucleotide position 217, causing the alanine (A) at amino acid position 73 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
10
DANN
Benign
0.87
Eigen
Benign
-0.054
Eigen_PC
Benign
0.015
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.42
T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.079
T;T
Sift4G
Benign
0.38
T;T
Vest4
0.11
MVP
0.093
ClinPred
0.24
T
GERP RS
3.3
gMVP
0.082

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117710538; API