19-9960686-C-A

Variant summary

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

The NM_015719.4(COL5A3):​c.5056G>T​(p.Ala1686Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,540 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

COL5A3
NM_015719.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.08
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]

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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=0.21779692).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A3NM_015719.4 linkc.5056G>T p.Ala1686Ser missense_variant Exon 66 of 67 ENST00000264828.4 NP_056534.2 P25940
COL5A3XM_011528042.3 linkc.5053G>T p.Ala1685Ser missense_variant Exon 66 of 67 XP_011526344.1
COL5A3XM_017026849.2 linkc.2719G>T p.Ala907Ser missense_variant Exon 39 of 40 XP_016882338.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A3ENST00000264828.4 linkc.5056G>T p.Ala1686Ser missense_variant Exon 66 of 67 1 NM_015719.4 ENSP00000264828.3 P25940

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461382
Hom.:
0
Cov.:
37
AF XY:
0.0000138
AC XY:
10
AN XY:
726992
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:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
15
DANN
Benign
0.15
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.27
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.29
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.20
N
REVEL
Benign
0.13
Sift
Benign
0.59
T
Sift4G
Benign
0.90
T
Polyphen
0.65
P
Vest4
0.24
MutPred
0.28
Gain of disorder (P = 0.0212);
MVP
0.59
MPC
0.32
ClinPred
0.23
T
GERP RS
4.0
Varity_R
0.062
gMVP
0.59

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

LitVar

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

Other links and lift over

dbSNP: rs779836383; hg19: chr19-10071362; API