dbSNP rs1457110544: COL5A1:p.Arg10Gly (chr9-134642215-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000093.5(COL5A1):c.28C>G(p.Arg10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. R10C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COL5A1
NM_000093.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

Publications

0 publications found

Variant links:

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Ehlers-Danlos syndrome, classic type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, PanelApp Australia, Genomics England PanelApp
Ehlers-Danlos syndrome, classic type, 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
arterial disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COL5A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2682858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
COL5A1	NM_000093.5 link	c.28C>G	p.Arg10Gly	missense_variant	Exon 1 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1 link	c.28C>G	p.Arg10Gly	missense_variant	Exon 1 of 66		NP_001265003.1
COL5A1	XM_017014266.3 link	c.28C>G	p.Arg10Gly	missense_variant	Exon 1 of 65		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.28C>G	p.Arg10Gly	missense_variant	Exon 1 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4 link	c.28C>G	p.Arg10Gly	missense_variant	Exon 1 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1154118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

560848

African (AFR)

AF:

0.00

AC:

AN:

23778

American (AMR)

AF:

0.00

AC:

AN:

18270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18382

East Asian (EAS)

AF:

0.00

AC:

AN:

24920

South Asian (SAS)

AF:

0.00

AC:

AN:

38856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3198

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

956310

Other (OTH)

AF:

0.00

AC:

AN:

45808

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.58

T;T

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.4

L;L

PhyloP100

0.084

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

N;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0080

D;.

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.19

B;.

Vest4

0.17

MutPred

0.43

Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);

MVP

0.62

MPC

0.25

ClinPred

0.54

GERP RS

1.4

PromoterAI

0.069

Neutral

(source)

Varity_R

0.094

gMVP

0.37

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over