9-134835184-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000093.5(COL5A1):​c.5350G>C​(p.Ala1784Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A1784T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

COL5A1
NM_000093.5 missense

Scores

5
5
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A1NM_000093.5 linkc.5350G>C p.Ala1784Pro missense_variant Exon 65 of 66 ENST00000371817.8 NP_000084.3 P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1NM_001278074.1 linkc.5350G>C p.Ala1784Pro missense_variant Exon 65 of 66 NP_001265003.1 B2ZZ86Q59EE7
LOC101448202NR_103451.2 linkn.71-14975C>G intron_variant Intron 1 of 1
COL5A1XM_017014266.3 linkc.*2431G>C downstream_gene_variant XP_016869755.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A1ENST00000371817.8 linkc.5350G>C p.Ala1784Pro missense_variant Exon 65 of 66 1 NM_000093.5 ENSP00000360882.3 P20908-1
COL5A1ENST00000371820.4 linkc.5350G>C p.Ala1784Pro missense_variant Exon 65 of 66 2 ENSP00000360885.4 P20908-2H7BY82

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461272
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726956
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.26
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.072
D
MetaRNN
Pathogenic
0.89
D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-2.3
N;.
REVEL
Pathogenic
0.69
Sift
Benign
0.15
T;.
Sift4G
Benign
0.18
T;T
Polyphen
1.0
D;.
Vest4
0.62
MutPred
0.82
Loss of stability (P = 0.0304);Loss of stability (P = 0.0304);
MVP
0.89
MPC
0.38
ClinPred
0.97
D
GERP RS
5.0
Varity_R
0.88
gMVP
0.82

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: chr9-137727030; API