NM_001680.5:c.*176T>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001680.5(FXYD2):​c.*176T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 167,860 control chromosomes in the GnomAD database, including 7,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6588 hom., cov: 32)
  • Exomes 𝑓: 0.33 (950 hom.)
• Consequence: FXYD2 NM_001680.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-117820203-A-C is Benign according to our data. Variant chr11-117820203-A-C is described in ClinVar as Benign. ClinVar VariationId is 302515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001680.5. 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
	FXYD2	NM_001680.5	MANE Select	c.*176T>G		3_prime_UTR	Exon 6 of 6	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.*176T>G		3_prime_UTR	Exon 11 of 11	NP_001191197.1	A0A087WZ82
	FXYD6-FXYD2	NM_001243598.4		c.*210T>G		3_prime_UTR	Exon 10 of 10	NP_001230527.1	A0A0A6YYL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	ENST00000292079.7	TSL:1 MANE Select	c.*176T>G		3_prime_UTR	Exon 6 of 6	ENSP00000292079.2	P54710-1
	FXYD2	ENST00000260287.2	TSL:1	c.*176T>G		3_prime_UTR	Exon 6 of 6	ENSP00000260287.2	P54710-2
	FXYD6-FXYD2	ENST00000532984.1	TSL:3	c.*210T>G		3_prime_UTR	Exon 10 of 10	ENSP00000463024.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41931 AN: 151986 Hom.: 6588 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.329 AC: 5183 AN: 15756 Hom.: 950 Cov.: 0 AF XY: 0.327 AC XY: 2617 AN XY: 8014

African (AFR) AF: 0.148 AC: 86 AN: 582

American (AMR) AF: 0.380 AC: 392 AN: 1032

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 196 AN: 520

East Asian (EAS) AF: 0.0845 AC: 61 AN: 722

South Asian (SAS) AF: 0.178 AC: 93 AN: 522

European-Finnish (FIN) AF: 0.310 AC: 311 AN: 1004

Middle Eastern (MID) AF: 0.227 AC: 15 AN: 66

European-Non Finnish (NFE) AF: 0.359 AC: 3691 AN: 10282

Other (OTH) AF: 0.329 AC: 338 AN: 1026

GnomAD4 genome AF: 0.276 AC: 41935 AN: 152104 Hom.: 6588 Cov.: 32 AF XY: 0.267 AC XY: 19871 AN XY: 74358

African (AFR) AF: 0.149 AC: 6201 AN: 41496

American (AMR) AF: 0.306 AC: 4678 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3470

East Asian (EAS) AF: 0.0951 AC: 492 AN: 5172

South Asian (SAS) AF: 0.168 AC: 811 AN: 4832

European-Finnish (FIN) AF: 0.319 AC: 3379 AN: 10580

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24281 AN: 67948

Other (OTH) AF: 0.276 AC: 584 AN: 2116

Alfa AF: 0.337 Hom.: 19758

Bravo AF: 0.273

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Renal hypomagnesemia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.52
PhyloP100		0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11999; hg19: chr11-117690918;