NM_054027.6:c.97-28360T>C

Variant names:

• chr5-14797551-A-G
• rs31989
• NM_054027.6:c.97-28360T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_054027.6(ANKH):​c.97-28360T>C variant causes a intron change. The variant allele was found at a frequency of 0.491 in 1,610,676 control chromosomes in the GnomAD database, including 198,323 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 0.50 (19285 hom., cov: 32)
  • Exomes 𝑓: 0.49 (179038 hom.)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.67
• Publications: 3 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]

RBBP4P1 (HGNC:42368): (RBBP4 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	NM_054027.6	MANE Select	c.97-28360T>C		intron	N/A	NP_473368.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	ENST00000284268.8	TSL:1 MANE Select	c.97-28360T>C		intron	N/A	ENSP00000284268.6
	ANKH	ENST00000887636.1		c.97-28360T>C		intron	N/A	ENSP00000557695.1
	ANKH	ENST00000964374.1		c.97-28360T>C		intron	N/A	ENSP00000634433.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75997 AN: 151928 Hom.: 19244 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.490 AC: 714605 AN: 1458630 Hom.: 179038 Cov.: 56 AF XY: 0.493 AC XY: 357717 AN XY: 725714

African (AFR) AF: 0.508 AC: 16972 AN: 33390

American (AMR) AF: 0.595 AC: 26617 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12254 AN: 26120

East Asian (EAS) AF: 0.796 AC: 31614 AN: 39700

South Asian (SAS) AF: 0.611 AC: 52596 AN: 86134

European-Finnish (FIN) AF: 0.438 AC: 23393 AN: 53416

Middle Eastern (MID) AF: 0.422 AC: 1747 AN: 4136

European-Non Finnish (NFE) AF: 0.468 AC: 519787 AN: 1110832

Other (OTH) AF: 0.492 AC: 29625 AN: 60186

GnomAD4 genome AF: 0.500 AC: 76094 AN: 152046 Hom.: 19285 Cov.: 32 AF XY: 0.503 AC XY: 37376 AN XY: 74316

African (AFR) AF: 0.510 AC: 21133 AN: 41442

American (AMR) AF: 0.561 AC: 8572 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3895 AN: 5178

South Asian (SAS) AF: 0.629 AC: 3030 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4422 AN: 10564

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31896 AN: 67966

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.491 Hom.: 2617

Bravo AF: 0.506

Asia WGS AF: 0.697 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.6
DANN	Benign	0.91
PhyloP100		6.7
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: rs31989; hg19: chr5-14797660;