19-9960686-C-G

Variant names:

• chr19-9960686-C-G
• rs779836383
• NM_015719.4:c.5056G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015719.4(COL5A3):​c.5056G>C​(p.Ala1686Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL5A3 NM_015719.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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]

ACMG classification

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=0.3001174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A3	NM_015719.4	c.5056G>C	p.Ala1686Pro	missense_variant	Exon 66 of 67	ENST00000264828.4	NP_056534.2
COL5A3	XM_011528042.3	c.5053G>C	p.Ala1685Pro	missense_variant	Exon 66 of 67		XP_011526344.1
COL5A3	XM_017026849.2	c.2719G>C	p.Ala907Pro	missense_variant	Exon 39 of 40		XP_016882338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A3	ENST00000264828.4	c.5056G>C	p.Ala1686Pro	missense_variant	Exon 66 of 67	1	NM_015719.4	ENSP00000264828.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249146 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135020

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: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461378 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 726992

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.: 32

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.0082	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.054
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.84	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.28
Sift	Benign	0.29	T
Sift4G	Benign	0.38	T
Polyphen		0.99	D
Vest4		0.19
MVP		0.74
MPC		0.45
ClinPred		0.43	T
GERP RS		4.0
Varity_R		0.19
gMVP		0.84

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

Other links and lift over

dbSNP: rs779836383; hg19: chr19-10071362;