chr6-75143335-T-G
Position:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS1
The NM_004370.6(COL12A1):āc.4744A>Cā(p.Met1582Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000674 in 1,613,882 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00039 ( 0 hom., cov: 32)
Exomes š: 0.00070 ( 1 hom. )
Consequence
COL12A1
NM_004370.6 missense
NM_004370.6 missense
Scores
1
4
10
Clinical Significance
Conservation
PhyloP100: 4.59
Genes affected
COL12A1 (HGNC:2188): (collagen type XII alpha 1 chain) This gene encodes the alpha chain of type XII collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XII collagen is a homotrimer found in association with type I collagen, an association that is thought to modify the interactions between collagen I fibrils and the surrounding matrix. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PP2
Missense variant where missense usually causes diseases, COL12A1
BP4
Computational evidence support a benign effect (MetaRNN=0.044110924).
BP6
Variant 6-75143335-T-G is Benign according to our data. Variant chr6-75143335-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 542494.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1, not_provided=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000394 (60/152228) while in subpopulation AMR AF= 0.00072 (11/15274). AF 95% confidence interval is 0.000494. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL12A1 | NM_004370.6 | c.4744A>C | p.Met1582Leu | missense_variant | 26/66 | ENST00000322507.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL12A1 | ENST00000322507.13 | c.4744A>C | p.Met1582Leu | missense_variant | 26/66 | 1 | NM_004370.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000394 AC: 60AN: 152228Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
60
AN:
152228
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000591 AC: 147AN: 248932Hom.: 0 AF XY: 0.000585 AC XY: 79AN XY: 135028
GnomAD3 exomes
AF:
AC:
147
AN:
248932
Hom.:
AF XY:
AC XY:
79
AN XY:
135028
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000703 AC: 1028AN: 1461654Hom.: 1 Cov.: 31 AF XY: 0.000662 AC XY: 481AN XY: 727118
GnomAD4 exome
AF:
AC:
1028
AN:
1461654
Hom.:
Cov.:
31
AF XY:
AC XY:
481
AN XY:
727118
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000394 AC: 60AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74364
GnomAD4 genome
AF:
AC:
60
AN:
152228
Hom.:
Cov.:
32
AF XY:
AC XY:
32
AN XY:
74364
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
3
ALSPAC
AF:
AC:
7
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
4
ExAC
AF:
AC:
90
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Bethlem myopathy 2;C4225314:Ullrich congenital muscular dystrophy 2 Uncertain:1Benign:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 09, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 04-23-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.0010, 0.0
.;B;B;.;.
Vest4
MutPred
0.55
.;Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
MPC
0.11
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at