9-134642239-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000093.5(COL5A1):c.52C>T(p.Pro18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 1,290,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

COL5A1
NM_000093.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 1.04

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10984516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A1	NM_000093.5	MANE Select	c.52C>T	p.Pro18Ser	missense	Exon 1 of 66	NP_000084.3
	COL5A1	NM_001278074.1		c.52C>T	p.Pro18Ser	missense	Exon 1 of 66	NP_001265003.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL5A1	ENST00000371817.8	TSL:1 MANE Select	c.52C>T	p.Pro18Ser	missense	Exon 1 of 66	ENSP00000360882.3
COL5A1	ENST00000371820.4	TSL:2	c.52C>T	p.Pro18Ser	missense	Exon 1 of 66	ENSP00000360885.4
COL5A1	ENST00000950240.1		c.52C>T	p.Pro18Ser	missense	Exon 1 of 66	ENSP00000620299.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150388

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000175

AC:

AN:

1139768

Hom.:

Cov.:

AF XY:

0.00000361

AC XY:

AN XY:

553512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23378

American (AMR)

AF:

0.00

AC:

AN:

17854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17950

East Asian (EAS)

AF:

0.00

AC:

AN:

23948

South Asian (SAS)

AF:

0.00

AC:

AN:

37882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3162

European-Non Finnish (NFE)

AF:

0.00000211

AC:

AN:

946888

Other (OTH)

AF:

0.00

AC:

AN:

44756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150388

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41174

American (AMR)

AF:

0.00

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

67438

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ehlers-Danlos syndrome, classic type, 1 (1)

Familial thoracic aortic aneurysm and aortic dissection (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.69

MutationAssessor

Benign

-0.60

PhyloP100

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.65

REVEL

Benign

0.15

Sift

Benign

0.92

Sift4G

Benign

0.89

Polyphen

0.0

Vest4

0.24

MutPred

0.23

Gain of phosphorylation at P18 (P = 0.0491)

MVP

0.27

MPC

0.20

ClinPred

0.45

GERP RS

0.70

PromoterAI

0.0092

Neutral

(source)

Varity_R

0.043

gMVP

0.49

Mutation Taster

=94/6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over