5-14816513-T-C

Variant names:

• chr5-14816513-T-C
• rs27353
• NM_054027.6:c.97-47322A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):​c.97-47322A>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
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	NM_054027.6	MANE Select	c.97-47322A>G		intron	N/A	NP_473368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	ENST00000284268.8	TSL:1 MANE Select	c.97-47322A>G		intron	N/A	ENSP00000284268.6
	ANKH	ENST00000513115.1	TSL:2	n.122-47322A>G		intron	N/A

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

African (AFR) AF: 0.444 AC: 18360 AN: 41396

American (AMR) AF: 0.536 AC: 8165 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3468

East Asian (EAS) AF: 0.752 AC: 3882 AN: 5160

South Asian (SAS) AF: 0.578 AC: 2784 AN: 4814

European-Finnish (FIN) AF: 0.399 AC: 4201 AN: 10528

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30588 AN: 67926

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.473 Hom.: 2961

Bravo AF: 0.474

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.49
PhyloP100		-2.5
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: rs27353; hg19: chr5-14816622;