chr10-70672863-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080722.4(ADAMTS14):​c.61G>A​(p.Ala21Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,501,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ADAMTS14
NM_080722.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.470
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038020402).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADAMTS14NM_080722.4 linkuse as main transcriptc.61G>A p.Ala21Thr missense_variant 1/22 ENST00000373207.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADAMTS14ENST00000373207.2 linkuse as main transcriptc.61G>A p.Ala21Thr missense_variant 1/221 NM_080722.4 P4Q8WXS8-1
ADAMTS14ENST00000373208.5 linkuse as main transcriptc.61G>A p.Ala21Thr missense_variant 1/222 A2Q8WXS8-4

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000103
AC:
1
AN:
97032
Hom.:
0
AF XY:
0.0000183
AC XY:
1
AN XY:
54586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000175
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000133
AC:
18
AN:
1348814
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
9
AN XY:
665594
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000964
Gnomad4 SAS exome
AF:
0.0000804
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.41e-7
Gnomad4 OTH exome
AF:
0.000143
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000134
AC:
1
Asia WGS
AF:
0.000579
AC:
2
AN:
3468

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 30, 2024The c.61G>A (p.A21T) alteration is located in exon 1 (coding exon 1) of the ADAMTS14 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the alanine (A) at amino acid position 21 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.37
T;T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.038
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N
MutationTaster
Benign
0.99
N;N
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.22
N;N
REVEL
Benign
0.041
Sift
Uncertain
0.019
D;D
Sift4G
Benign
0.38
T;T
Polyphen
0.016
.;B
Vest4
0.24
MutPred
0.28
Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP
0.47
MPC
0.16
ClinPred
0.051
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.055
gMVP
0.50

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: rs372953443; hg19: chr10-72432619; API