5-14824063-T-G

Position:

• chr5-14824063-T-G

Variant summary

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

The NM_054027.6(ANKH):​c.96+47289A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,060 control chromosomes in the GnomAD database, including 5,705 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 0.27 (5705 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150

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]

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 (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.96+47289A>C		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.96+47289A>C		intron_variant			XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.96+47289A>C		intron_variant		1	NM_054027.6	ENSP00000284268	P1
ANKH	ENST00000513115.1	n.121+47289A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40901 AN: 151942 Hom.: 5698 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.269 AC: 40934 AN: 152060 Hom.: 5705 Cov.: 32 AF XY: 0.267 AC XY: 19877 AN XY: 74318

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.246

Alfa AF: 0.259 Hom.: 2781

Bravo AF: 0.269

Asia WGS AF: 0.261 AC: 910 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	3.8
DANN	Benign	0.53

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: rs398961; hg19: chr5-14824172;