rs4938445

Variant names:

• chr11-117874288-G-A
• rs4938445
• NM_022003.4:c.-6+2304C>T

Variant summary

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

The NM_022003.4(FXYD6):​c.-6+2304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,078 control chromosomes in the GnomAD database, including 8,132 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 0.32 (8132 hom., cov: 32)
• Consequence: FXYD6 NM_022003.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 10 publications found

Genes affected

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FXYD6	NM_022003.4	c.-6+2304C>T		intron_variant	Intron 1 of 7	ENST00000526014.6	NP_071286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FXYD6	ENST00000526014.6	c.-6+2304C>T		intron_variant	Intron 1 of 7	1	NM_022003.4	ENSP00000433312.1
FXYD6-FXYD2	ENST00000614497.5	c.-6+2304C>T		intron_variant	Intron 1 of 10	3		ENSP00000482442.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49384 AN: 151960 Hom.: 8133 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.325 AC: 49403 AN: 152078 Hom.: 8132 Cov.: 32 AF XY: 0.325 AC XY: 24149 AN XY: 74344

African (AFR) AF: 0.357 AC: 14809 AN: 41452

American (AMR) AF: 0.265 AC: 4045 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3470

East Asian (EAS) AF: 0.163 AC: 846 AN: 5178

South Asian (SAS) AF: 0.285 AC: 1371 AN: 4816

European-Finnish (FIN) AF: 0.369 AC: 3904 AN: 10574

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

European-Non Finnish (NFE) AF: 0.324 AC: 22058 AN: 67990

Other (OTH) AF: 0.306 AC: 647 AN: 2112

Alfa AF: 0.319 Hom.: 19630

Bravo AF: 0.316

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.77
PhyloP100		-0.95
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

Other links and lift over

dbSNP: rs4938445; hg19: chr11-117745003;