rs153931

Positions:

• chr5-14742193-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_054027.6(ANKH):​c.916-271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,076 control chromosomes in the GnomAD database, including 11,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.35 (11474 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.87

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-14742193-T-C is Benign according to our data. Variant chr5-14742193-T-C is described in ClinVar as [Benign]. Clinvar id is 1247050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.916-271A>G		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.916-271A>G		intron_variant			XP_011512369.1
ANKH	XM_017009644.3	c.832-271A>G		intron_variant			XP_016865133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.916-271A>G		intron_variant		1	NM_054027.6	ENSP00000284268	P1
ANKH	ENST00000503939.5	n.428-271A>G		intron_variant, non_coding_transcript_variant		3
ANKH	ENST00000515517.1	n.150-271A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52991 AN: 151958 Hom.: 11437 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.349 AC: 53079 AN: 152076 Hom.: 11474 Cov.: 32 AF XY: 0.341 AC XY: 25329 AN XY: 74328

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.327

Alfa AF: 0.308 Hom.: 1088

Bravo AF: 0.372

Asia WGS AF: 0.160 AC: 559 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.048
DANN	Benign	0.35

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: rs153931; hg19: chr5-14742302;