Variant 6-56077539-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030820.4(COL21A1):c.1847T>C(p.Met616Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 1,427,050 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: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

COL21A1
NM_030820.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

COL21A1 (HGNC:17025): (collagen type XXI alpha 1 chain) This gene encodes the alpha chain of type XXI collagen, a member of the FACIT (fibril-associated collagens with interrupted helices) collagen family. Type XXI collagen is localized to tissues containing type I collagen and maintains the integrity of the extracellular matrix. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

COL21A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23924708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL21A1	NM_030820.4 linkuse as main transcript	c.1847T>C	p.Met616Thr	missense_variant	18/30	ENST00000244728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL21A1	ENST00000244728.10 linkuse as main transcript	c.1847T>C	p.Met616Thr	missense_variant	18/30	1	NM_030820.4	A1	Q96P44-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000920

AC:

AN:

217472

Hom.:

AF XY:

0.0000170

AC XY:

AN XY:

117666

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:

0.0000772

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000841

AC:

AN:

1427050

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

708580

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:

0.0000998

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000832

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

Jan 04, 2024

The c.1847T>C (p.M616T) alteration is located in exon 18 (coding exon 17) of the COL21A1 gene. This alteration results from a T to C substitution at nucleotide position 1847, causing the methionine (M) at amino acid position 616 to be replaced by a threonine (T). 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

0.087

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0066

T;.;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.47

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.50

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.20

N;N;.

REVEL

Benign

0.087

Sift

Benign

0.42

T;T;.

Sift4G

Benign

0.57

T;T;T

Polyphen

0.081

B;.;.

Vest4

0.46

MutPred

0.33

Gain of phosphorylation at M616 (P = 0.0175);.;.;

MVP

0.21

MPC

0.020

ClinPred

0.15

GERP RS

5.1

Varity_R

0.074

gMVP

0.20

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