19-9960551-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015719.4(COL5A3):ā€‹c.5098A>Gā€‹(p.Lys1700Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00024 ( 0 hom., cov: 32)
Exomes š‘“: 0.000047 ( 0 hom. )

Consequence

COL5A3
NM_015719.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.055515498).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A3NM_015719.4 linkc.5098A>G p.Lys1700Glu missense_variant Exon 67 of 67 ENST00000264828.4 NP_056534.2 P25940
COL5A3XM_011528042.3 linkc.5095A>G p.Lys1699Glu missense_variant Exon 67 of 67 XP_011526344.1
COL5A3XM_017026849.2 linkc.2761A>G p.Lys921Glu missense_variant Exon 40 of 40 XP_016882338.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A3ENST00000264828.4 linkc.5098A>G p.Lys1700Glu missense_variant Exon 67 of 67 1 NM_015719.4 ENSP00000264828.3 P25940

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000845
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000717
AC:
18
AN:
251214
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.000865
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000465
AC:
68
AN:
1461882
Hom.:
0
Cov.:
41
AF XY:
0.0000399
AC XY:
29
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00122
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000236
AC:
36
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000500
Hom.:
0
Bravo
AF:
0.000355
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5098A>G (p.K1700E) alteration is located in exon 67 (coding exon 67) of the COL5A3 gene. This alteration results from a A to G substitution at nucleotide position 5098, causing the lysine (K) at amino acid position 1700 to be replaced by a glutamic acid (E). 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
0.26
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.32
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-0.47
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.22
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.019
D
Polyphen
0.21
B
Vest4
0.32
MVP
0.67
MPC
0.49
ClinPred
0.14
T
GERP RS
3.0
Varity_R
0.60
gMVP
0.54

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: rs141809828; hg19: chr19-10071227; API