6-75194844-C-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_004370.6(COL12A1):​c.177G>T​(p.Val59Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V59V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COL12A1
NM_004370.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.452

Publications

0 publications found
Variant links:
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]
COL12A1 Gene-Disease associations (from GenCC):
  • Bethlem myopathy 2
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
  • Bethlem myopathy 2
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Illumina, Genomics England PanelApp
  • Ullrich congenital muscular dystrophy 2
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • Bethlem myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Ullrich congenital muscular dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP7
Synonymous conserved (PhyloP=0.452 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL12A1NM_004370.6 linkc.177G>T p.Val59Val synonymous_variant Exon 3 of 66 ENST00000322507.13 NP_004361.3 Q99715-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL12A1ENST00000322507.13 linkc.177G>T p.Val59Val synonymous_variant Exon 3 of 66 1 NM_004370.6 ENSP00000325146.8 Q99715-1
COL12A1ENST00000345356.10 linkc.73+7876G>T intron_variant Intron 2 of 50 1 ENSP00000305147.9 Q99715-2
COL12A1ENST00000483888.6 linkc.177G>T p.Val59Val synonymous_variant Exon 3 of 65 5 ENSP00000421216.1 D6RGG3
COL12A1ENST00000416123.6 linkc.177G>T p.Val59Val synonymous_variant Exon 2 of 63 5 ENSP00000412864.2 Q99715-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1456324
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
724554
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33276
American (AMR)
AF:
0.00
AC:
0
AN:
44320
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26042
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39564
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85282
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53358
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1108514
Other (OTH)
AF:
0.00
AC:
0
AN:
60212
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
10
DANN
Benign
0.87
PhyloP100
0.45

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

Other links and lift over

dbSNP: rs772158281; hg19: chr6-75904560; API