2-188974519-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_000090.4(COL3A1):c.30G>C(p.Trp10Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: COL3A1 NM_000090.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.40

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, COL3A1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL3A1	NM_000090.4	c.30G>C	p.Trp10Cys	missense_variant	1/51	ENST00000304636.9
LOC105373791	XR_007087614.1	n.110-4040C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL3A1	ENST00000304636.9	c.30G>C	p.Trp10Cys	missense_variant	1/51	1	NM_000090.4	P1
COL3A1	ENST00000450867.2	c.30G>C	p.Trp10Cys	missense_variant	1/50	1
COL3A1	ENST00000470167.1	n.126G>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, type 4 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

All of Us Research Program, National Institutes of Health

Mar 04, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.91	P;.
Vest4		0.67
MutPred		0.51		Gain of catalytic residue at L11 (P = 0.0107);Gain of catalytic residue at L11 (P = 0.0107);
MVP		0.74
MPC		0.99
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.78

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: chr2-189839245;