Variant 1-31661692-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.3694C>T(p.Pro1232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COL16A1
NM_001856.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

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:

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=0.32656467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL16A1	NM_001856.4 link	c.3694C>T	p.Pro1232Ser	missense_variant	59/71	ENST00000373672.8	NP_001847.3	Q07092-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL16A1	ENST00000373672.8 link	c.3694C>T	p.Pro1232Ser	missense_variant	59/71	5	NM_001856.4	ENSP00000362776.3		Q07092-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448928

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720978

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

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

Oct 01, 2024

The c.3694C>T (p.P1232S) alteration is located in exon 59 (coding exon 58) of the COL16A1 gene. This alteration results from a C to T substitution at nucleotide position 3694, causing the proline (P) at amino acid position 1232 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

0.094

BayesDel_addAF

Uncertain

0.077

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.33

T;T

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

1.6

L;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.80

N;N

REVEL

Uncertain

0.32

Sift

Benign

0.24

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.81

P;.

Vest4

0.33

MutPred

0.34

Gain of phosphorylation at P1232 (P = 0.0065);.;

MVP

0.84

MPC

0.16

ClinPred

0.71

GERP RS

4.6

Varity_R

0.059

gMVP

0.30

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