Variant 1-31658490-G-A 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.4018C>T(p.Pro1340Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,446,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

COL16A1
NM_001856.4 missense, splice_region

Scores

Splicing: ADA: 0.5901

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.30

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:

COL16A1 (HGNC:):

COL16A1 links:

Genome browser will be placed here

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=0.34997886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL16A1	NM_001856.4 linkuse as main transcript	c.4018C>T	p.Pro1340Ser	missense_variant, splice_region_variant	64/71	ENST00000373672.8	NP_001847.3	Q07092-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL16A1	ENST00000373672.8 linkuse as main transcript	c.4018C>T	p.Pro1340Ser	missense_variant, splice_region_variant	64/71	5	NM_001856.4	ENSP00000362776.3		Q07092-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000224

AC:

AN:

222994

Hom.:

AF XY:

0.00000830

AC XY:

AN XY:

120452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000969

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000622

AC:

AN:

1446504

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

718118

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000167

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

Aug 01, 2024

The c.4018C>T (p.P1340S) alteration is located in exon 64 (coding exon 63) of the COL16A1 gene. This alteration results from a C to T substitution at nucleotide position 4018, causing the proline (P) at amino acid position 1340 to be replaced by a serine (S). 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

0.097

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.015

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.87

D;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.35

T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Benign

1.5

L;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.37

Sift

Benign

0.031

D;D

Sift4G

Benign

0.26

T;T

Polyphen

0.0080

B;.

Vest4

0.35

MutPred

0.37

Gain of phosphorylation at P1340 (P = 0.0077);.;

MVP

0.83

MPC

0.16

ClinPred

0.12

GERP RS

2.7

Varity_R

0.067

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.59

dbscSNV1_RF

Benign

0.50

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