1-103078818-C-T

Position:

• chr1-103078818-C-T

Variant summary

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

The NM_001854.4(COL11A1):​c.328G>A​(p.Gly110Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL11A1 NM_001854.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

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 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/exons	MANE	UniProt
COL11A1	NM_001854.4	c.328G>A	p.Gly110Arg	missense_variant	3/67	ENST00000370096.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL11A1	ENST00000370096.9	c.328G>A	p.Gly110Arg	missense_variant	3/67	1	NM_001854.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Connective tissue disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Nov 01, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.;.;.;.;.;.;.;.;D
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.74	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;M;M;M;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.0	D;D;D;D;.;.;.;.;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D;D;D;D;.;.;.;.;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;.;.;.;.;.;D
Polyphen		1.0	D;D;D;.;.;.;.;.;.;.
Vest4		0.81
MutPred		0.29		Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);.;
MVP		0.57
MPC		0.62
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.69
gMVP		0.46

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: rs141978499; hg19: chr1-103544374; COSMIC: COSV62183153;