chr8-120162499-G-T

Variant names:

• chr8-120162499-G-T
• NM_021110.4:c.279G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021110.4(COL14A1):​c.279G>T​(p.Gln93His) 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. 13/22 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: COL14A1 NM_021110.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28977293).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	NM_021110.4	MANE Select	c.279G>T	p.Gln93His	missense	Exon 4 of 48	NP_066933.1	Q05707-1
	COL14A1	NM_001413492.1		c.279G>T	p.Gln93His	missense	Exon 4 of 48	NP_001400421.1
	COL14A1	NM_001413490.1		c.279G>T	p.Gln93His	missense	Exon 4 of 48	NP_001400419.1	Q05707-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL14A1	ENST00000297848.8	TSL:5 MANE Select	c.279G>T	p.Gln93His	missense	Exon 4 of 48	ENSP00000297848.3	Q05707-1
	COL14A1	ENST00000432943.6	TSL:1	n.513G>T		non_coding_transcript_exon	Exon 4 of 27
	COL14A1	ENST00000498051.6	TSL:1	n.279G>T		non_coding_transcript_exon	Exon 7 of 23	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.24
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Benign	0.078	T
Sift4G	Uncertain	0.030	D
Polyphen		0.97	D
Vest4		0.55
MutPred		0.48		Gain of catalytic residue at N94 (P = 0.0527)
MVP		0.51
MPC		0.64
ClinPred		0.85	D
GERP RS		4.7
Varity_R		0.13
gMVP		0.65
Mutation Taster		=58/42	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: chr8-121174738;