rs2086745052

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015719.4(COL5A3):​c.4718G>A​(p.Arg1573Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

COL5A3
NM_015719.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26
Variant links:
Genes affected
COL5A3 (HGNC:14864): (collagen type V alpha 3 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. Mutations in this gene are thought to be responsible for the symptoms of a subset of patients with Ehlers-Danlos syndrome type III. Messages of several sizes can be detected in northern blots but sequence information cannot confirm the identity of the shorter messages. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.093939334).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A3NM_015719.4 linkc.4718G>A p.Arg1573Lys missense_variant Exon 64 of 67 ENST00000264828.4 NP_056534.2 P25940
COL5A3XM_011528042.3 linkc.4715G>A p.Arg1572Lys missense_variant Exon 64 of 67 XP_011526344.1
COL5A3XM_017026849.2 linkc.2381G>A p.Arg794Lys missense_variant Exon 37 of 40 XP_016882338.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A3ENST00000264828.4 linkc.4718G>A p.Arg1573Lys missense_variant Exon 64 of 67 1 NM_015719.4 ENSP00000264828.3 P25940

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1457846
Hom.:
0
Cov.:
32
AF XY:
0.00000276
AC XY:
2
AN XY:
724690
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4718G>A (p.R1573K) alteration is located in exon 64 (coding exon 64) of the COL5A3 gene. This alteration results from a G to A substitution at nucleotide position 4718, causing the arginine (R) at amino acid position 1573 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
17
DANN
Benign
0.94
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.49
N
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.56
N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.34
N
REVEL
Benign
0.10
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0020
B
Vest4
0.097
MutPred
0.54
Gain of methylation at R1573 (P = 0.0144);
MVP
0.53
MPC
0.35
ClinPred
0.38
T
GERP RS
2.1
Varity_R
0.099
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2086745052; hg19: chr19-10077054; API