9-134815627-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000093.5(COL5A1):​c.4066G>T​(p.Ala1356Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COL5A1
NM_000093.5 missense, splice_region

Scores

6
13
Splicing: ADA: 0.03165
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38350552).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL5A1NM_000093.5 linkc.4066G>T p.Ala1356Ser missense_variant, splice_region_variant 51/66 ENST00000371817.8 NP_000084.3 P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1NM_001278074.1 linkc.4066G>T p.Ala1356Ser missense_variant, splice_region_variant 51/66 NP_001265003.1 B2ZZ86Q59EE7
COL5A1XM_017014266.3 linkc.4066G>T p.Ala1356Ser missense_variant, splice_region_variant 51/65 XP_016869755.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL5A1ENST00000371817.8 linkc.4066G>T p.Ala1356Ser missense_variant, splice_region_variant 51/661 NM_000093.5 ENSP00000360882.3 P20908-1
COL5A1ENST00000371820.4 linkc.4066G>T p.Ala1356Ser missense_variant, splice_region_variant 51/662 ENSP00000360885.4 P20908-2H7BY82

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248348
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461328
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726908
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:
0.00
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
0.074
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.078
T;.
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.0057
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.83
T;T
M_CAP
Uncertain
0.097
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Uncertain
-0.11
T
MutationAssessor
Benign
0.60
N;N
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.25
N;.
REVEL
Uncertain
0.39
Sift
Benign
0.74
T;.
Sift4G
Benign
0.89
T;T
Polyphen
0.35
B;.
Vest4
0.40
MutPred
0.30
Gain of phosphorylation at A1356 (P = 0.0019);Gain of phosphorylation at A1356 (P = 0.0019);
MVP
0.56
MPC
0.27
ClinPred
0.83
D
GERP RS
5.2
Varity_R
0.084
gMVP
0.10

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.032
dbscSNV1_RF
Benign
0.13
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: rs147868179; hg19: chr9-137707473; API