chr6-56124109-G-C

Position:

• chr6-56124109-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030820.4(COL21A1):​c.1711C>G​(p.Pro571Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COL21A1 NM_030820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL21A1	NM_030820.4	c.1711C>G	p.Pro571Ala	missense_variant	16/30	ENST00000244728.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL21A1	ENST00000244728.10	c.1711C>G	p.Pro571Ala	missense_variant	16/30	1	NM_030820.4	A1
COL21A1	ENST00000370819.5	c.1702C>G	p.Pro568Ala	missense_variant	15/29	1		P4
COL21A1	ENST00000488912.5	c.103C>G	p.Pro35Ala	missense_variant, NMD_transcript_variant	3/18	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Uncertain	0.72	D
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	0.55	D;D;D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Pathogenic	0.65
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.15	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.33
MutPred		0.52		Loss of methylation at K576 (P = 0.073);.;.;
MVP		0.60
MPC		0.067
ClinPred		0.93	D
GERP RS		3.4
Varity_R		0.11
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-55988907;