rs11289042

Variant names:

• chr6-75087281-GAAA-G
• rs11289042
• NM_004370.6:c.9181+293_9181+295delTTT

Your query was ambiguous. Multiple possible variants found:

• chr6-75087281-GAAA-G
• chr6-75087281-GAAA-GA
• chr6-75087281-GAAA-GAA
• chr6-75087281-GAAA-GAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004370.6(COL12A1):​c.9181+293_9181+295delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 154,600 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL12A1 NM_004370.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.554
• 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: Orphanet, Labcorp Genetics (formerly Invitae)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004370.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL12A1	NM_004370.6	MANE Select	c.9181+293_9181+295delTTT		intron	N/A	NP_004361.3
	COL12A1	NM_001424113.1		c.9181+293_9181+295delTTT		intron	N/A	NP_001411042.1
	COL12A1	NM_001424114.1		c.9160+293_9160+295delTTT		intron	N/A	NP_001411043.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL12A1	ENST00000322507.13	TSL:1 MANE Select	c.9181+293_9181+295delTTT		intron	N/A	ENSP00000325146.8	Q99715-1
	COL12A1	ENST00000345356.10	TSL:1	c.5689+293_5689+295delTTT		intron	N/A	ENSP00000305147.9	Q99715-2
	COL12A1	ENST00000483888.6	TSL:5	c.*273_*275delTTT		3_prime_UTR	Exon 65 of 65	ENSP00000421216.1	D6RGG3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 150694 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 2 AN: 154600 Hom.: 0 AF XY: 0.0000255 AC XY: 2 AN XY: 78282

⚠️ 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: 4572

American (AMR) AF: 0.00 AC: 0 AN: 5218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5882

East Asian (EAS) AF: 0.00 AC: 0 AN: 13100

South Asian (SAS) AF: 0.00 AC: 0 AN: 3332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 844

European-Non Finnish (NFE) AF: 0.0000200 AC: 2 AN: 100110

Other (OTH) AF: 0.00 AC: 0 AN: 10530

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 150694 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73474

African (AFR) AF: 0.00 AC: 0 AN: 40990

American (AMR) AF: 0.00 AC: 0 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67696

Other (OTH) AF: 0.00 AC: 0 AN: 2070

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11289042; hg19: chr6-75796997;