6-75102607-G-C

Variant names:

• chr6-75102607-G-C
• NM_004370.6:c.8405C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004370.6(COL12A1):​c.8405C>G​(p.Pro2802Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,036 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: COL12A1 NM_004370.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.8405C>G	p.Pro2802Arg	missense_variant	Exon 56 of 66	ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.8405C>G	p.Pro2802Arg	missense_variant	Exon 56 of 66	1	NM_004370.6	ENSP00000325146.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396036 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 694108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	.;T;T;.;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.5	.;.;M;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.5	N;.;N;N;N;N
REVEL	Pathogenic	0.65
Sift	Benign	0.53	T;.;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T;T
Polyphen		1.0	.;.;D;D;.;.
Vest4		0.41, 0.55, 0.53, 0.50, 0.46
MutPred		0.50		.;.;Gain of MoRF binding (P = 0.0137);.;.;Gain of MoRF binding (P = 0.0137);
MVP		0.74
MPC		1.4
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.26
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-75812323;