rs754587593

Variant names:

• chr6-75138928-G-A
• NM_004370.6:c.4991C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-75138928-G-A
• chr6-75138928-G-T

Variant summary

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

The NM_004370.6(COL12A1):​c.4991C>T​(p.Thr1664Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 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: 0.0000014 (0 hom.)
• Consequence: COL12A1 NM_004370.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.43

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.4991C>T	p.Thr1664Ile	missense_variant	Exon 28 of 66	ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.4991C>T	p.Thr1664Ile	missense_variant	Exon 28 of 66	1	NM_004370.6	ENSP00000325146.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727190

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: 0.00000180

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	0.25
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T;T;.;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T;T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	.;M;.;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	.;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.010	.;D;T;D;D
Sift4G	Uncertain	0.020	D;D;D;D;D
Polyphen		0.86, 0.72	.;P;P;.;.
Vest4		0.52
MutPred		0.60		.;Loss of glycosylation at T1664 (P = 0.0158);.;Loss of glycosylation at T1664 (P = 0.0158);Loss of glycosylation at T1664 (P = 0.0158);
MVP		0.39
MPC		0.38
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.21
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-75848644;