6-75086648-GTATATATATATATA-G

Variant names:

• chr6-75086648-GTATATATATATATA-G
• rs61611291
• NM_004370.6:c.9182-105_9182-92delTATATATATATATA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004370.6(COL12A1):​c.9182-105_9182-92delTATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000679 in 147,326 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: COL12A1 NM_004370.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.991
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.9182-105_9182-92delTATATATATATATA		intron_variant	Intron 65 of 65	ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.9182-105_9182-92delTATATATATATATA		intron_variant	Intron 65 of 65	1	NM_004370.6	ENSP00000325146.8

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000679 AC: 1 AN: 147326 Hom.: 0 AF XY: 0.0000122 AC XY: 1 AN XY: 82126

African (AFR) AF: 0.00 AC: 0 AN: 2548

American (AMR) AF: 0.00 AC: 0 AN: 6466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4274

East Asian (EAS) AF: 0.00 AC: 0 AN: 5768

South Asian (SAS) AF: 0.00 AC: 0 AN: 12824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 544

European-Non Finnish (NFE) AF: 0.0000112 AC: 1 AN: 89132

Other (OTH) AF: 0.00 AC: 0 AN: 6522

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 1017

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61611291; hg19: chr6-75796364;