rs10899795

chr10-43373649-C-Achr10-43373649-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173160.3(FXYD4):c.-98C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 786,940 control chromosomes in the GnomAD database, including 33,873 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 (8722 hom., cov: 32)
  • Exomes 𝑓: 0.27 (25151 hom.)
• Consequence: FXYD4 NM_173160.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

Genes affected

FXYD4 (HGNC:4028): (FXYD domain containing ion transport regulator 4) This gene encodes a member of a family of small membrane proteins that share a 35-amino acid signature sequence domain, beginning with the sequence PFXYD and containing 7 invariant and 6 highly conserved amino acids. The approved human gene nomenclature for the family is FXYD-domain containing ion transport regulator. FXYD4, originally named CHIF for channel-inducing factor, has been shown to modulate the properties of the Na,K-ATPase, as has FXYD2, also known as the gamma subunit of the Na,K-ATPase, and FXYD7. Transmembrane topology has been established for FXYD4 and two family members (FXYD1 and FXYD2), with the N-terminus extracellular and the C-terminus on the cytoplasmic side of the membrane. Alternatively spliced transcript variants encoding the same protein have been found.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FXYD4	NM_173160.3	c.-98C>A		5_prime_UTR_variant	3/9	ENST00000476166.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXYD4	ENST00000476166.6	c.-98C>A		5_prime_UTR_variant	3/9	1	NM_173160.3	P1
FXYD4	ENST00000616495.1	c.-98C>A		5_prime_UTR_variant	2/8	5		P1
FXYD4	ENST00000480834.5	n.92-821C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48658 AN: 151898 Hom.: 8702 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.271 AC: 172125 AN: 634924 Hom.: 25151 Cov.: 7 AF XY: 0.274 AC XY: 94284 AN XY: 343638

Gnomad4 AFR exome AF: 0.491

Gnomad4 AMR exome AF: 0.272

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.321 AC: 48723 AN: 152016 Hom.: 8722 Cov.: 32 AF XY: 0.326 AC XY: 24218 AN XY: 74314

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.289

Alfa AF: 0.240 Hom.: 8538

Bravo AF: 0.326

Asia WGS AF: 0.388 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	18
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.98		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.98		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10899795; hg19: chr10-43869097; COSMIC: COSV101519294; COSMIC: COSV101519294;