chr19-9966378-C-G

Variant names:

• chr19-9966378-C-G
• rs2086745052
• NM_015719.4:c.4718G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015719.4(COL5A3):​c.4718G>C​(p.Arg1573Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1573K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: COL5A3 NM_015719.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

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]

ENSG00000295554 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3813165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015719.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A3	NM_015719.4	MANE Select	c.4718G>C	p.Arg1573Thr	missense	Exon 64 of 67	NP_056534.2	P25940

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A3	ENST00000264828.4	TSL:1 MANE Select	c.4718G>C	p.Arg1573Thr	missense	Exon 64 of 67	ENSP00000264828.3	P25940
	ENSG00000295554	ENST00000730923.1		n.74-17672C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457846 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724690

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25896

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109628

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.0040
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.3
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.64	P
Vest4		0.38
MutPred		0.58		Loss of catalytic residue at R1573 (P = 0.0453)
MVP		0.77
MPC		0.52
ClinPred		0.94	D
GERP RS		2.1
Varity_R		0.52
gMVP		0.74
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2086745052; hg19: chr19-10077054;