NM_021110.4:c.275A>G

Variant names:

• chr8-120162495-A-G
• rs554596714
• NM_021110.4:c.275A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021110.4(COL14A1):​c.275A>G​(p.Asp92Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000996 in 1,613,182 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (22 hom.)
• Consequence: COL14A1 NM_021110.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.35
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00811559).
• BP6: Variant 8-120162495-A-G is Benign according to our data. Variant chr8-120162495-A-G is described in ClinVar as Benign. ClinVar VariationId is 723311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 86 AD gene.

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.275A>G	p.Asp92Gly	missense	Exon 4 of 48	NP_066933.1	Q05707-1
	COL14A1	NM_001413492.1		c.275A>G	p.Asp92Gly	missense	Exon 4 of 48	NP_001400421.1
	COL14A1	NM_001413490.1		c.275A>G	p.Asp92Gly	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.275A>G	p.Asp92Gly	missense	Exon 4 of 48	ENSP00000297848.3	Q05707-1
	COL14A1	ENST00000432943.6	TSL:1	n.509A>G		non_coding_transcript_exon	Exon 4 of 27
	COL14A1	ENST00000498051.6	TSL:1	n.275A>G		non_coding_transcript_exon	Exon 7 of 23	ENSP00000428851.1	Q4G0W3

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152236 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00207 AC: 518 AN: 250100 AF XY: 0.00278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000986

GnomAD4 exome AF: 0.00104 AC: 1520 AN: 1460828 Hom.: 22 Cov.: 30 AF XY: 0.00150 AC XY: 1093 AN XY: 726648

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.000112 AC: 5 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.0155 AC: 1333 AN: 85820

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53396

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.0000828 AC: 92 AN: 1111626

Other (OTH) AF: 0.00123 AC: 74 AN: 60372

GnomAD4 genome AF: 0.000564 AC: 86 AN: 152354 Hom.: 3 Cov.: 33 AF XY: 0.000886 AC XY: 66 AN XY: 74498

African (AFR) AF: 0.0000240 AC: 1 AN: 41580

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000183 Hom.: 0

Bravo AF: 0.000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00244 AC: 296

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.48
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.75	N
PhyloP100		6.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.17
Sift	Benign	0.69	T
Sift4G	Benign	0.26	T
Polyphen		0.58	P
Vest4		0.39
MVP		0.43
MPC		0.46
ClinPred		0.052	T
GERP RS		5.6
Varity_R		0.17
gMVP		0.44
Mutation Taster		=96/4	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

dbSNP: rs554596714; hg19: chr8-121174734;