chr5-33576092-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030955.4(ADAMTS12):​c.3934C>A​(p.His1312Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ADAMTS12
NM_030955.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81
Variant links:
Genes affected
ADAMTS12 (HGNC:14605): (ADAM metallopeptidase with thrombospondin type 1 motif 12) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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-1) motif. Individual members of this family differ in the number of C-terminal TS-1 motifs, and some have unique C-terminal domains. The enzyme encoded by this gene contains eight TS-1 motifs. It may play roles in pulmonary cells during fetal development or in tumor processes through its proteolytic activity or as a molecule potentially involved in regulation of cell adhesion. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13934168).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAMTS12NM_030955.4 linkuse as main transcriptc.3934C>A p.His1312Asn missense_variant 19/24 ENST00000504830.6 NP_112217.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMTS12ENST00000504830.6 linkuse as main transcriptc.3934C>A p.His1312Asn missense_variant 19/241 NM_030955.4 ENSP00000422554 P1P58397-1
ADAMTS12ENST00000352040.7 linkuse as main transcriptc.3679C>A p.His1227Asn missense_variant 17/221 ENSP00000344847 P58397-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 GeneticsNov 06, 2023The c.3934C>A (p.H1312N) alteration is located in exon 19 (coding exon 19) of the ADAMTS12 gene. This alteration results from a C to A substitution at nucleotide position 3934, causing the histidine (H) at amino acid position 1312 to be replaced by an asparagine (N). 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
0.063
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
5.8
DANN
Benign
0.41
DEOGEN2
Benign
0.028
T;.
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.082
Sift
Benign
0.57
T;T
Sift4G
Benign
0.58
T;T
Polyphen
0.20
B;B
Vest4
0.29
MutPred
0.44
Gain of loop (P = 0.1069);.;
MVP
0.54
MPC
0.17
ClinPred
0.21
T
GERP RS
4.7
Varity_R
0.14
gMVP
0.19

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: rs1746694284; hg19: chr5-33576197; API