chr9-98985745-G-A

Variant names:

• chr9-98985745-G-A
• NM_001855.5:c.281G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001855.5(COL15A1):​c.281G>A​(p.Ser94Asn) 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. 15/22 in silico tools predict a benign outcome for this variant. 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: 1.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2462022).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001855.5. 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
	COL15A1	NM_001855.5	MANE Select	c.281G>A	p.Ser94Asn	missense	Exon 3 of 42	NP_001846.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL15A1	ENST00000375001.8	TSL:1 MANE Select	c.281G>A	p.Ser94Asn	missense	Exon 3 of 42	ENSP00000364140.3	P39059
	COL15A1	ENST00000946050.1		c.281G>A	p.Ser94Asn	missense	Exon 3 of 42	ENSP00000616109.1
	COL15A1	ENST00000873223.1		c.281G>A	p.Ser94Asn	missense	Exon 3 of 42	ENSP00000543282.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.24
Sift	Benign	0.36	T
Sift4G	Benign	0.38	T
Polyphen		0.99	D
Vest4		0.41
MutPred		0.41		Loss of sheet (P = 0.0817)
MVP		0.81
MPC		0.17
ClinPred		0.49	T
GERP RS		4.3
Varity_R		0.075
gMVP		0.34
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr9-101748027;