NM_080680.3:c.3932A>C

Variant names:

• chr6-33168547-T-G
• NM_080680.3:c.3932A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080680.3(COL11A2):​c.3932A>C​(p.Asn1311Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COL11A2 NM_080680.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

Genes affected

COL11A2 (HGNC:2187): (collagen type XI alpha 2 chain) This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. It is located on chromosome 6 very close to but separate from the gene for retinoid X receptor beta. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Proteolytic processing of this type XI chain produces PARP, a proline/arginine-rich protein that is an amino terminal domain. Mutations in this gene are associated with type III Stickler syndrome, otospondylomegaepiphyseal dysplasia (OSMED syndrome), Weissenbacher-Zweymuller syndrome, autosomal dominant non-syndromic sensorineural type 13 deafness (DFNA13), and autosomal recessive non-syndromic sensorineural type 53 deafness (DFNB53). Alternative splicing results in multiple transcript variants. A related pseudogene is located nearby on chromosome 6. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3221709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL11A2	NM_080680.3	c.3932A>C	p.Asn1311Thr	missense_variant	Exon 54 of 66	ENST00000341947.7	NP_542411.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL11A2	ENST00000341947.7	c.3932A>C	p.Asn1311Thr	missense_variant	Exon 54 of 66	5	NM_080680.3	ENSP00000339915.2
COL11A2	ENST00000374708.8	c.3674A>C	p.Asn1225Thr	missense_variant	Exon 52 of 64	5		ENSP00000363840.4
COL11A2	ENST00000477772.1	n.273-2731A>C		intron_variant	Intron 5 of 8	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461454 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727042

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0081	T;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.030
FATHMM_MKL	Benign	0.73	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Uncertain	-0.18	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.66	N;N;N
REVEL	Uncertain	0.39
Sift	Benign	0.55	T;T;T
Sift4G	Benign	0.29	T;T;T
Vest4		0.43
MutPred		0.25		.;Gain of phosphorylation at N1311 (P = 0.0013);.;
MVP		0.80
MPC		0.34
ClinPred		0.72	D
GERP RS		4.3
gMVP		0.43

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: chr6-33136324;