rs10513186

Positions:

• chr5-14765553-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):​c.313+3422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,968 control chromosomes in the GnomAD database, including 2,040 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 0.15 (2040 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.313+3422G>A		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.313+3422G>A		intron_variant			XP_011512369.1
ANKH	XM_017009644.3	c.229+3422G>A		intron_variant			XP_016865133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.313+3422G>A		intron_variant		1	NM_054027.6	ENSP00000284268	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23339 AN: 151850 Hom.: 2034 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.154 AC: 23364 AN: 151968 Hom.: 2040 Cov.: 32 AF XY: 0.152 AC XY: 11318 AN XY: 74246

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0332

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.205

Alfa AF: 0.186 Hom.: 2580

Bravo AF: 0.149

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.50

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: rs10513186; hg19: chr5-14765662;