NM_001856.4:c.4733G>A

Variant names:

• chr1-31652733-C-T
• NM_001856.4:c.4733G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001856.4(COL16A1):​c.4733G>A​(p.Cys1578Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL16A1 NM_001856.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61
• Publications: 0 publications found

Genes affected

COL16A1 (HGNC:2193): (collagen type XVI alpha 1 chain) This gene encodes the alpha chain of type XVI collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). 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. High levels of type XVI collagen have been found in fibroblasts and keratinocytes, and in smooth muscle and amnion. [provided by RefSeq, Jul 2008]

PEF1-AS1 (HGNC:40154): (PEF1 and COL16A1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001856.4. 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
	COL16A1	NM_001856.4	MANE Select	c.4733G>A	p.Cys1578Tyr	missense	Exon 71 of 71	NP_001847.3
	PEF1-AS1	NR_184311.1		n.436+745C>T		intron	N/A
	PEF1-AS1	NR_184312.1		n.436+745C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL16A1	ENST00000373672.8	TSL:5 MANE Select	c.4733G>A	p.Cys1578Tyr	missense	Exon 71 of 71	ENSP00000362776.3	Q07092-1
	COL16A1	ENST00000488897.5	TSL:1	n.2278G>A		non_coding_transcript_exon	Exon 15 of 15
	COL16A1	ENST00000873809.1		c.4688G>A	p.Cys1563Tyr	missense	Exon 70 of 70	ENSP00000543868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0085	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		5.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.52	N
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.39		Gain of phosphorylation at C1578 (P = 0.0051)
MVP		0.94
MPC		0.88
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.62
gMVP		0.94
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr1-32118334;