5-14811536-A-T

Variant names:

• chr5-14811536-A-T
• rs31912
• NM_054027.6:c.97-42345T>A

Variant summary

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

The NM_054027.6(ANKH):​c.97-42345T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,036 control chromosomes in the GnomAD database, including 29,653 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 0.62 (29653 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-42345T>A		intron_variant	Intron 1 of 11	ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.97-42345T>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.97-42345T>A		intron_variant	Intron 1 of 11	1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000513115.1	n.122-42345T>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94167 AN: 151918 Hom.: 29598 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.620 AC: 94286 AN: 152036 Hom.: 29653 Cov.: 32 AF XY: 0.625 AC XY: 46431 AN XY: 74310

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.673

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.571

Alfa AF: 0.605 Hom.: 3504

Bravo AF: 0.624

Asia WGS AF: 0.768 AC: 2672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
DANN	Benign	0.81

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: rs31912; hg19: chr5-14811645;