11-117820203-A-T

Variant names:

• chr11-117820203-A-T
• rs11999
• NM_001680.5:c.*176T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001680.5(FXYD2):​c.*176T>A variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FXYD2 NM_001680.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 7 publications found

Genes affected

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]

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]

ENSG00000254844 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD2	NM_001680.5	c.*176T>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000292079.7	NP_001671.2
FXYD6-FXYD2	NM_001204268.3	c.*176T>A		3_prime_UTR_variant	Exon 11 of 11		NP_001191197.1
FXYD6-FXYD2	NM_001243598.4	c.*210T>A		3_prime_UTR_variant	Exon 10 of 10		NP_001230527.1
FXYD2	NM_021603.4	c.*176T>A		3_prime_UTR_variant	Exon 6 of 6		NP_067614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD2	ENST00000292079.7	c.*176T>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_001680.5	ENSP00000292079.2
FXYD6-FXYD2	ENST00000614497.5	c.*176T>A		downstream_gene_variant		3		ENSP00000482442.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 15816 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8040

African (AFR) AF: 0.00 AC: 0 AN: 584

American (AMR) AF: 0.00 AC: 0 AN: 1044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 520

East Asian (EAS) AF: 0.00 AC: 0 AN: 722

South Asian (SAS) AF: 0.00 AC: 0 AN: 526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 66

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10314

Other (OTH) AF: 0.00 AC: 0 AN: 1034

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs11999; hg19: chr11-117690918;