rs140250347

Variant names:

• chr1-102879759-C-G
• NM_001854.4:c.5198G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-102879759-C-G
• chr1-102879759-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_001854.4(COL11A1):​c.5198G>C​(p.Arg1733Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1733H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: COL11A1 NM_001854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13

Genes affected

COL11A1 (HGNC:2186): (collagen type XI alpha 1 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Mutations in this gene are associated with type II Stickler syndrome and with Marshall syndrome. A single-nucleotide polymorphism in this gene is also associated with susceptibility to lumbar disc herniation. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-102879760-G-A is described in Lovd as [Likely_pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A1	NM_001854.4	c.5198G>C	p.Arg1733Pro	missense_variant	Exon 66 of 67	ENST00000370096.9	NP_001845.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A1	ENST00000370096.9	c.5198G>C	p.Arg1733Pro	missense_variant	Exon 66 of 67	1	NM_001854.4	ENSP00000359114.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	D;.;.;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Pathogenic	3.4	M;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-5.0	D;D;D;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.95
MutPred		0.65		Loss of stability (P = 0.0556);.;.;.;
MVP		0.93
MPC		0.17
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.92
gMVP		0.91

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: chr1-103345315; COSMIC: COSV62186732;