9-98985766-G-A

Variant names:

• chr9-98985766-G-A
• rs368284198
• NM_001855.5:c.302G>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.302G>A​(p.Ser101Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. S101T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL15A1 NM_001855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 3 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=0.18735138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL15A1	NM_001855.5	c.302G>A	p.Ser101Asn	missense_variant	Exon 3 of 42	ENST00000375001.8	NP_001846.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL15A1	ENST00000375001.8	c.302G>A	p.Ser101Asn	missense_variant	Exon 3 of 42	1	NM_001855.5	ENSP00000364140.3
COL15A1	ENST00000471477.1	n.725G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251106 AF XY: 0.00000737

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M;.
PhyloP100		4.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.093
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.012	D;D
Polyphen		0.33	B;.
Vest4		0.36
MutPred		0.38		Loss of disorder (P = 0.0992);.;
MVP		0.43
MPC		0.11
ClinPred		0.58	D
GERP RS		4.4
Varity_R		0.11
gMVP		0.13
Mutation Taster		=88/12	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

dbSNP: rs368284198; hg19: chr9-101748048;