NM_054027.6:c.97-7597G>A

Variant names:

• chr5-14776788-C-T
• rs17251763
• NM_054027.6:c.97-7597G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• chondrocalcinosis 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• craniometaphyseal dysplasia, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• skeletal dysplasia

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• craniometaphyseal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-7597G>A		intron_variant	Intron 1 of 11	ENST00000284268.8	NP_473368.1
ANKH	XM_017009644.3	c.13-7597G>A		intron_variant	Intron 1 of 11		XP_016865133.1
ANKH	XM_011514067.2	c.97-7597G>A		intron_variant	Intron 1 of 8		XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.97-7597G>A		intron_variant	Intron 1 of 11	1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000503389.1	n.103-7597G>A		intron_variant	Intron 1 of 1	3
ANKH	ENST00000513115.1	n.122-7597G>A		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.151 AC: 6274 AN: 41530

American (AMR) AF: 0.334 AC: 5111 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1571 AN: 5176

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4822

European-Finnish (FIN) AF: 0.296 AC: 3125 AN: 10558

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20035 AN: 67982

Other (OTH) AF: 0.234 AC: 493 AN: 2106

Alfa AF: 0.280 Hom.: 20682

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
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17251763; hg19: chr5-14776897;