5-14783123-C-G

Variant names:

• chr5-14783123-C-G
• rs25957
• NM_054027.6:c.97-13932G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):​c.97-13932G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,994 control chromosomes in the GnomAD database, including 45,241 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 0.77 (45241 hom., cov: 30)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 7 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]

ANKH Gene-Disease associations (from GenCC):

• chondrocalcinosis 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• craniometaphyseal dysplasia, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• skeletal dysplasia

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• craniometaphyseal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-13932G>C		intron_variant	Intron 1 of 11	ENST00000284268.8	NP_473368.1
ANKH	XM_017009644.3	c.12+13095G>C		intron_variant	Intron 1 of 11		XP_016865133.1
ANKH	XM_011514067.2	c.97-13932G>C		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.97-13932G>C		intron_variant	Intron 1 of 11	1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000503389.1	n.102+4993G>C		intron_variant	Intron 1 of 1	3
ANKH	ENST00000513115.1	n.122-13932G>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117042 AN: 151878 Hom.: 45183 Cov.: 30

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.771 AC: 117160 AN: 151994 Hom.: 45241 Cov.: 30 AF XY: 0.775 AC XY: 57579 AN XY: 74296

African (AFR) AF: 0.755 AC: 31280 AN: 41426

American (AMR) AF: 0.806 AC: 12310 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2408 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4338 AN: 5168

South Asian (SAS) AF: 0.857 AC: 4127 AN: 4816

European-Finnish (FIN) AF: 0.800 AC: 8445 AN: 10560

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51800 AN: 67968

Other (OTH) AF: 0.762 AC: 1610 AN: 2114

Alfa AF: 0.782 Hom.: 5775

Bravo AF: 0.765

Asia WGS AF: 0.840 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.75
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: rs25957; hg19: chr5-14783232;