rs3006069

chr5-14869600-A-Gchr5-14869600-A-T

Variant summary

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

The NM_054027.6(ANKH):c.96+1752T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,114 control chromosomes in the GnomAD database, including 15,464 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 0.45 (15464 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856

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 = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.96+1752T>C		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.96+1752T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.96+1752T>C		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000647541.1	n.763T>C		non_coding_transcript_exon_variant	1/1
ANKH	ENST00000505140.1	c.*885-570T>C		intron_variant, NMD_transcript_variant		5
ANKH	ENST00000513115.1	n.121+1752T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68189 AN: 151996 Hom.: 15459 Cov.: 33

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.473

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.449 AC: 68232 AN: 152114 Hom.: 15464 Cov.: 33 AF XY: 0.445 AC XY: 33115 AN XY: 74366

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.467

Alfa AF: 0.465 Hom.: 18621

Bravo AF: 0.454

Asia WGS AF: 0.359 AC: 1247 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	5.7
Dann	Benign	0.82

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: rs3006069; hg19: chr5-14869709;