NM_001680.5:c.*1C>T

Variant names:

• chr11-117820671-G-A
• rs869789
• NM_001680.5:c.*1C>T

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.*1C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,726 control chromosomes in the GnomAD database, including 15,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1373 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14620 hom.)
• Consequence: FXYD2 NM_001680.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.527
• Publications: 15 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 11-117820671-G-A is Benign according to our data. Variant chr11-117820671-G-A is described in ClinVar as Benign. ClinVar VariationId is 302521.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 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.*1C>T		3_prime_UTR	Exon 5 of 6	NP_001671.2
	FXYD6-FXYD2	NM_001204268.3		c.*1C>T		3_prime_UTR	Exon 10 of 11	NP_001191197.1
	FXYD6-FXYD2	NM_001243598.4		c.*35C>T		3_prime_UTR	Exon 9 of 10	NP_001230527.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXYD2	ENST00000292079.7	TSL:1 MANE Select	c.*1C>T		3_prime_UTR	Exon 5 of 6	ENSP00000292079.2
	FXYD6-FXYD2	ENST00000614497.5	TSL:3	c.*1C>T		3_prime_UTR	Exon 10 of 11	ENSP00000482442.1
	FXYD2	ENST00000260287.2	TSL:1	c.*1C>T		3_prime_UTR	Exon 5 of 6	ENSP00000260287.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19627 AN: 152052 Hom.: 1370 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.139 AC: 34821 AN: 250982 AF XY: 0.131

Gnomad AFR exome AF: 0.0888

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.190

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.137 AC: 200385 AN: 1461556 Hom.: 14620 Cov.: 33 AF XY: 0.134 AC XY: 97090 AN XY: 727110

African (AFR) AF: 0.0930 AC: 3112 AN: 33466

American (AMR) AF: 0.225 AC: 10047 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3022 AN: 26132

East Asian (EAS) AF: 0.216 AC: 8561 AN: 39698

South Asian (SAS) AF: 0.0445 AC: 3840 AN: 86252

European-Finnish (FIN) AF: 0.134 AC: 7169 AN: 53334

Middle Eastern (MID) AF: 0.144 AC: 832 AN: 5764

European-Non Finnish (NFE) AF: 0.140 AC: 155379 AN: 1111822

Other (OTH) AF: 0.139 AC: 8423 AN: 60382

GnomAD4 genome AF: 0.129 AC: 19650 AN: 152170 Hom.: 1373 Cov.: 32 AF XY: 0.129 AC XY: 9565 AN XY: 74374

African (AFR) AF: 0.0931 AC: 3864 AN: 41522

American (AMR) AF: 0.178 AC: 2716 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.191 AC: 987 AN: 5168

South Asian (SAS) AF: 0.0447 AC: 216 AN: 4830

European-Finnish (FIN) AF: 0.127 AC: 1347 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9614 AN: 67982

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.134 Hom.: 3050

Bravo AF: 0.136

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.67
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs869789; hg19: chr11-117691386; COSMIC: COSV52643034; COSMIC: COSV52643034;