rs2288474
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_054027.6(ANKH):c.963A>G(p.Ala321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,613,956 control chromosomes in the GnomAD database, including 3,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.064 ( 420 hom., cov: 33)
Exomes 𝑓: 0.052 ( 2710 hom. )
Consequence
ANKH
NM_054027.6 synonymous
NM_054027.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.92
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 5-14741875-T-C is Benign according to our data. Variant chr5-14741875-T-C is described in ClinVar as [Benign]. Clinvar id is 351512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.92 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKH | NM_054027.6 | c.963A>G | p.Ala321= | synonymous_variant | 8/12 | ENST00000284268.8 | |
ANKH | XM_017009644.3 | c.879A>G | p.Ala293= | synonymous_variant | 8/12 | ||
ANKH | XM_011514067.2 | c.963A>G | p.Ala321= | synonymous_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKH | ENST00000284268.8 | c.963A>G | p.Ala321= | synonymous_variant | 8/12 | 1 | NM_054027.6 | P1 | |
ANKH | ENST00000503939.5 | n.475A>G | non_coding_transcript_exon_variant | 5/6 | 3 | ||||
ANKH | ENST00000515517.1 | n.197A>G | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0636 AC: 9676AN: 152136Hom.: 416 Cov.: 33
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GnomAD3 exomes AF: 0.0704 AC: 17709AN: 251412Hom.: 978 AF XY: 0.0647 AC XY: 8796AN XY: 135878
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GnomAD4 exome AF: 0.0516 AC: 75462AN: 1461702Hom.: 2710 Cov.: 31 AF XY: 0.0511 AC XY: 37153AN XY: 727154
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GnomAD4 genome ? AF: 0.0637 AC: 9697AN: 152254Hom.: 420 Cov.: 33 AF XY: 0.0639 AC XY: 4758AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Craniometaphyseal dysplasia, autosomal dominant Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Chondrocalcinosis 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at