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10-70674989-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_080722.4(ADAMTS14):c.516C>T(p.Asp172=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,611,926 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00077 ( 5 hom. )

Consequence

ADAMTS14
NM_080722.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49
Variant links:
Genes affected
ADAMTS14 (HGNC:14899): (ADAM metallopeptidase with thrombospondin type 1 motif 14) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-70674989-C-T is Benign according to our data. Variant chr10-70674989-C-T is described in ClinVar as [Benign]. Clinvar id is 786164.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.49 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0056 (853/152304) while in subpopulation AFR AF= 0.019 (788/41550). AF 95% confidence interval is 0.0179. There are 6 homozygotes in gnomad4. There are 394 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAMTS14NM_080722.4 linkuse as main transcriptc.516C>T p.Asp172= synonymous_variant 2/22 ENST00000373207.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAMTS14ENST00000373207.2 linkuse as main transcriptc.516C>T p.Asp172= synonymous_variant 2/221 NM_080722.4 P4Q8WXS8-1
ADAMTS14ENST00000373208.5 linkuse as main transcriptc.516C>T p.Asp172= synonymous_variant 2/222 A2Q8WXS8-4

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00556
AC:
846
AN:
152186
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0189
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00222
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00145
AC:
359
AN:
247298
Hom.:
2
AF XY:
0.00118
AC XY:
159
AN XY:
134386
show subpopulations
Gnomad AFR exome
AF:
0.0182
Gnomad AMR exome
AF:
0.000608
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000687
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000278
Gnomad OTH exome
AF:
0.000659
GnomAD4 exome
AF:
0.000770
AC:
1124
AN:
1459622
Hom.:
5
Cov.:
32
AF XY:
0.000697
AC XY:
506
AN XY:
726062
show subpopulations
Gnomad4 AFR exome
AF:
0.0176
Gnomad4 AMR exome
AF:
0.000738
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000800
Gnomad4 FIN exome
AF:
0.0000195
Gnomad4 NFE exome
AF:
0.000322
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00560
AC:
853
AN:
152304
Hom.:
6
Cov.:
33
AF XY:
0.00529
AC XY:
394
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0190
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00315
Hom.:
3
Bravo
AF:
0.00673
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
3.9
Dann
Benign
0.68

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144956824; hg19: chr10-72434745; API