5-14749019-C-T

Variant names:

• chr5-14749019-C-T
• rs13170282
• NM_054027.6:c.822+153G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_054027.6(ANKH):​c.822+153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,222 control chromosomes in the GnomAD database, including 1,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1796 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-14749019-C-T is Benign according to our data. Variant chr5-14749019-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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.822+153G>A		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.822+153G>A		intron	N/A	ENSP00000284268.6
	ANKH	ENST00000887636.1		c.822+153G>A		intron	N/A	ENSP00000557695.1
	ANKH	ENST00000964374.1		c.822+153G>A		intron	N/A	ENSP00000634433.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19404 AN: 152104 Hom.: 1793 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0399

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.128 AC: 19441 AN: 152222 Hom.: 1796 Cov.: 33 AF XY: 0.125 AC XY: 9282 AN XY: 74420

African (AFR) AF: 0.254 AC: 10550 AN: 41518

American (AMR) AF: 0.149 AC: 2274 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3470

East Asian (EAS) AF: 0.130 AC: 672 AN: 5186

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4822

European-Finnish (FIN) AF: 0.0399 AC: 423 AN: 10600

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0690 AC: 4694 AN: 68012

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.127 Hom.: 339

Bravo AF: 0.143

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.61
PhyloP100		-1.9
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: rs13170282; hg19: chr5-14749128; COSMIC: COSV52479471;