rs886038544

Variant names:

• chr6-75183111-A-C
• rs886038544
• NM_004370.6:c.1830T>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_004370.6(COL12A1):​c.1830T>G​(p.Phe610Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL12A1 NM_004370.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.92

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39374402).
• BP6: Variant 6-75183111-A-C is Benign according to our data. Variant chr6-75183111-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 259320.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL12A1	NM_004370.6	c.1830T>G	p.Phe610Leu	missense_variant	Exon 10 of 66	ENST00000322507.13	NP_004361.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL12A1	ENST00000322507.13	c.1830T>G	p.Phe610Leu	missense_variant	Exon 10 of 66	1	NM_004370.6	ENSP00000325146.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.080	N;N;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.90	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.73	P;.;P
Vest4		0.57
MutPred		0.51		Loss of catalytic residue at F610 (P = 0.0341);Loss of catalytic residue at F610 (P = 0.0341);Loss of catalytic residue at F610 (P = 0.0341);
MVP		0.69
MPC		0.61
ClinPred		0.45	T
GERP RS		5.7
Varity_R		0.29
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs886038544; hg19: chr6-75892827;