5-14776788-C-T

Position:

• chr5-14776788-C-T

Variant summary

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

The NM_054027.6(ANKH):​c.97-7597G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,134 control chromosomes in the GnomAD database, including 5,440 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 0.26 (5440 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

Genes affected

ANKH (HGNC:15492): (ANKH inorganic pyrophosphate transport regulator) This gene encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Progressive ankylosis-mediated control of pyrophosphate levels has been suggested as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. Mutations in this gene have been associated with autosomal dominant craniometaphyseal dysplasia. [provided by RefSeq, Jul 2008]

ANKH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-7597G>A		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_017009644.3	c.13-7597G>A		intron_variant			XP_016865133.1
ANKH	XM_011514067.2	c.97-7597G>A		intron_variant			XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.97-7597G>A		intron_variant		1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000503389.1	n.103-7597G>A		intron_variant		3
ANKH	ENST00000513115.1	n.122-7597G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39233 AN: 152016 Hom.: 5442 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.258 AC: 39245 AN: 152134 Hom.: 5440 Cov.: 33 AF XY: 0.258 AC XY: 19200 AN XY: 74368

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.234

Alfa AF: 0.278 Hom.: 7475

Bravo AF: 0.253

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.7
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs17251763; hg19: chr5-14776897;