rs534898281

Variant names:

• chr2-188984952-C-G
• rs534898281
• NM_000090.4:c.272C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-188984952-C-G
• chr2-188984952-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP2

The NM_000090.4(COL3A1):​c.272C>G​(p.Pro91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P91L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL3A1 NM_000090.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403

Genes affected

COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]

LOC105373791 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the COL3A1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 495 curated pathogenic missense variants (we use a threshold of 10). The gene has 19 curated benign missense variants. Gene score misZ: 4.0879 (above the threshold of 3.09). Trascript score misZ: 4.5995 (above the threshold of 3.09). GenCC associations: The gene is linked to Ehlers-Danlos syndrome, vascular type, autosomal dominant Ehlers-Danlos syndrome, vascular type, polymicrogyria with or without vascular-type Ehlers-Danlos syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL3A1	NM_000090.4	c.272C>G	p.Pro91Arg	missense_variant	Exon 2 of 51	ENST00000304636.9	NP_000081.2
LOC105373791	XR_007087614.1	n.-133G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL3A1	ENST00000304636.9	c.272C>G	p.Pro91Arg	missense_variant	Exon 2 of 51	1	NM_000090.4	ENSP00000304408.4
COL3A1	ENST00000450867.2	c.272C>G	p.Pro91Arg	missense_variant	Exon 2 of 50	1		ENSP00000415346.2
COL3A1	ENST00000470167.1	n.368C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460664 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726670

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33444

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44580

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26096

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39674

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86240

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53258

Gnomad4 NFE exome AF: 9.00e-7 AC: 1 AN: 1111292

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.63	T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.40
Sift	Benign	0.67	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.31	B;.
Vest4		0.41
MutPred		0.45		Loss of glycosylation at P91 (P = 0.0084);Loss of glycosylation at P91 (P = 0.0084);
MVP		0.66
MPC		0.66
ClinPred		0.46	T
GERP RS		4.4
Varity_R		0.13
gMVP		0.23
Mutation Taster		=78/22	polymorphism

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: rs534898281; hg19: chr2-189849678;