5-14749019-C-T

Position:

• chr5-14749019-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.822+153G>A		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.822+153G>A		intron_variant
ANKH	XM_017009644.3	c.738+153G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.822+153G>A		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000503939.5	n.334+153G>A		intron_variant, non_coding_transcript_variant		3
ANKH	ENST00000515517.1	n.56+153G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.0399

Gnomad4 NFE AF: 0.0690

Gnomad4 OTH AF: 0.118

Alfa AF: 0.124 Hom.: 313

Bravo AF: 0.143

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.61

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: rs13170282; hg19: chr5-14749128; COSMIC: COSV52479471;