5-14816513-T-C

Variant summary

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

The NM_054027.6(ANKH):c.97-47322A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,842 control chromosomes in the GnomAD database, including 16,893 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 0.47 (16893 hom., cov: 31)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.97-47322A>G		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.97-47322A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.97-47322A>G		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000513115.1	n.122-47322A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70956 AN: 151722 Hom.: 16857 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.468 AC: 71042 AN: 151842 Hom.: 16893 Cov.: 31 AF XY: 0.469 AC XY: 34764 AN XY: 74186

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.439

Alfa AF: 0.474 Hom.: 2878

Bravo AF: 0.474

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.14
Dann	Benign	0.49

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: rs27353; hg19: chr5-14816622;