chr8-120313981-C-T

Variant names:

• chr8-120313981-C-T
• rs397514597
• NM_021110.4:c.4505C>T

Variant summary

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

The NM_021110.4(COL14A1):​c.4505C>T​(p.Pro1502Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL14A1 NM_021110.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.73
• Publications: 2 publications found

Genes affected

COL14A1 (HGNC:2191): (collagen type XIV alpha 1 chain) This gene encodes the alpha chain of type XIV collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XIV collagen interacts with the fibril surface and is involved in the regulation of fibrillogenesis. [provided by RefSeq, Jan 2013]

COL14A1 Gene-Disease associations (from GenCC):

• punctate palmoplantar keratoderma type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary palmoplantar keratoderma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021110.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	NM_021110.4	MANE Select	c.4505C>T	p.Pro1502Leu	missense	Exon 38 of 48	NP_066933.1
	COL14A1	NM_001413492.1		c.4505C>T	p.Pro1502Leu	missense	Exon 38 of 48	NP_001400421.1
	COL14A1	NM_001413490.1		c.4505C>T	p.Pro1502Leu	missense	Exon 38 of 48	NP_001400419.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	ENST00000297848.8	TSL:5 MANE Select	c.4505C>T	p.Pro1502Leu	missense	Exon 38 of 48	ENSP00000297848.3
	COL14A1	ENST00000309791.8	TSL:5	c.4505C>T	p.Pro1502Leu	missense	Exon 38 of 48	ENSP00000311809.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Variant of unknown significance Uncertain:1

Sep 01, 2012

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.096	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Benign	1.1	L
PhyloP100		2.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.60
Sift	Benign	0.058	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.77
MutPred		0.39		Loss of glycosylation at P1502 (P = 0.0263)
MVP		0.89
MPC		0.77
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.29
gMVP		0.72
Mutation Taster		=1/99	disease causing

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

dbSNP: rs397514597; hg19: chr8-121326220;