6-69929488-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001858.6(COL19A1):c.454G>A(p.Asp152Asn) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL19A1 NM_001858.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

Genes affected

COL19A1 (HGNC:2196): (collagen type XIX alpha 1 chain) This gene encodes the alpha chain of type XIX collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Although the function of this collagen is not known, other members of this collagen family are found in association with fibril-forming collagens such as type I and II, and serve to maintain the integrity of the extracellular matrix. The transcript produced from this gene has an unusually large 3' UTR which has not been completely sequenced. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13110724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL19A1	NM_001858.6	c.454G>A	p.Asp152Asn	missense_variant	6/51	ENST00000620364.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL19A1	ENST00000620364.5	c.454G>A	p.Asp152Asn	missense_variant	6/51	1	NM_001858.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 13, 2023

The c.454G>A (p.D152N) alteration is located in exon 6 (coding exon 5) of the COL19A1 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the aspartic acid (D) at amino acid position 152 to be replaced by an asparagine (N). 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	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	18
Dann	Benign	0.97
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.60	D
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.23	T
Polyphen		0.0050	B
Vest4		0.17
MutPred		0.47		Loss of catalytic residue at A148 (P = 0.3251);
MVP		0.58
ClinPred		0.48	T
GERP RS		3.5
Varity_R		0.037
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1772610834; hg19: chr6-70639380;