5-14780189-C-T

Variant names:

• chr5-14780189-C-T
• rs17317655
• NM_054027.6:c.97-10998G>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.97-10998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,804 control chromosomes in the GnomAD database, including 2,246 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 0.16 (2246 hom., cov: 30)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-10998G>A		intron_variant	Intron 1 of 11	ENST00000284268.8	NP_473368.1
ANKH	XM_017009644.3	c.13-10998G>A		intron_variant	Intron 1 of 11		XP_016865133.1
ANKH	XM_011514067.2	c.97-10998G>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.97-10998G>A		intron_variant	Intron 1 of 11	1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000503389.1	n.102+7927G>A		intron_variant	Intron 1 of 1	3
ANKH	ENST00000513115.1	n.122-10998G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24044 AN: 151686 Hom.: 2244 Cov.: 30

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.158 AC: 24056 AN: 151804 Hom.: 2246 Cov.: 30 AF XY: 0.158 AC XY: 11709 AN XY: 74170

African (AFR) AF: 0.0773 AC: 3199 AN: 41392

American (AMR) AF: 0.144 AC: 2189 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3470

East Asian (EAS) AF: 0.0260 AC: 134 AN: 5154

South Asian (SAS) AF: 0.243 AC: 1166 AN: 4802

European-Finnish (FIN) AF: 0.171 AC: 1797 AN: 10494

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14209 AN: 67938

Other (OTH) AF: 0.203 AC: 426 AN: 2096

Alfa AF: 0.198 Hom.: 2229

Bravo AF: 0.150

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.69
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: rs17317655; hg19: chr5-14780298;