9-98985672-G-C

Position:

• chr9-98985672-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001855.5(COL15A1):​c.208G>C​(p.Gly70Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL15A1 NM_001855.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

Genes affected

COL15A1 (HGNC:2192): (collagen type XV alpha 1 chain) This gene encodes the alpha chain of type XV collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Type XV collagen has a wide tissue distribution but the strongest expression is localized to basement membrane zones so it may function to adhere basement membranes to underlying connective tissue stroma. The proteolytically produced C-terminal fragment of type XV collagen is restin, a potentially antiangiogenic protein that is closely related to endostatin. Mouse studies have shown that collagen XV deficiency is associated with muscle and microvessel deterioration. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL15A1	NM_001855.5	c.208G>C	p.Gly70Arg	missense_variant	3/42	ENST00000375001.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL15A1	ENST00000375001.8	c.208G>C	p.Gly70Arg	missense_variant	3/42	1	NM_001855.5	P1
COL15A1	ENST00000471477.1	n.631G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.208G>C (p.G70R) alteration is located in exon 3 (coding exon 3) of the COL15A1 gene. This alteration results from a G to C substitution at nucleotide position 208, causing the glycine (G) at amino acid position 70 to be replaced by an arginine (R). 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	0.20
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Uncertain	0.30
Sift	Benign	0.062	T;.
Sift4G	Benign	0.066	T;T
Polyphen		0.78	P;.
Vest4		0.42
MutPred		0.47		Gain of methylation at G70 (P = 0.0134);.;
MVP		0.81
MPC		0.15
ClinPred		0.88	D
GERP RS		3.4
Varity_R		0.15
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-101747954;