Variant 1-31666066-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001856.4(COL16A1):c.3373G>A(p.Glu1125Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

COL16A1
NM_001856.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

Variant links:

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]

COL16A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL16A1	NM_001856.4 linkuse as main transcript	c.3373G>A	p.Glu1125Lys	missense_variant	53/71	ENST00000373672.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL16A1	ENST00000373672.8 linkuse as main transcript	c.3373G>A	p.Glu1125Lys	missense_variant	53/71	5	NM_001856.4	P1	Q07092-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247066

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1459966

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.3373G>A (p.E1125K) alteration is located in exon 53 (coding exon 52) of the COL16A1 gene. This alteration results from a G to A substitution at nucleotide position 3373, causing the glutamic acid (E) at amino acid position 1125 to be replaced by a lysine (K). 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

0.14

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0051

T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.88

D;D

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.28

T;T

MetaSVM

Uncertain

-0.013

MutationAssessor

Benign

-0.91

N;.

MutationTaster

Benign

0.77

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.090

N;N

REVEL

Uncertain

0.42

Sift

Benign

0.24

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.46

P;.

Vest4

0.50

MutPred

0.37

Gain of methylation at E1125 (P = 0.0029);.;

MVP

0.75

MPC

0.18

ClinPred

0.25

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over