NM_030820.4:c.1886G>A

Variant names:

• chr6-56075504-C-T
• rs1313458713
• NM_030820.4:c.1886G>A
• COL21A1 p.Gly629Glu

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_030820.4(COL21A1):​c.1886G>A​(p.Gly629Glu) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL21A1 NM_030820.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.987

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL21A1	NM_030820.4	MANE Select	c.1886G>A	p.Gly629Glu	missense	Exon 19 of 30	NP_110447.2
	COL21A1	NM_001318751.2		c.1886G>A	p.Gly629Glu	missense	Exon 20 of 31	NP_001305680.1	Q96P44-1
	COL21A1	NM_001318752.2		c.1877G>A	p.Gly626Glu	missense	Exon 18 of 29	NP_001305681.1	Q96P44-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL21A1	ENST00000244728.10	TSL:1 MANE Select	c.1886G>A	p.Gly629Glu	missense	Exon 19 of 30	ENSP00000244728.5	Q96P44-1
	COL21A1	ENST00000370819.5	TSL:1	c.1877G>A	p.Gly626Glu	missense	Exon 18 of 29	ENSP00000359855.1	Q96P44-3
	COL21A1	ENST00000488912.5	TSL:1	n.*134G>A		non_coding_transcript_exon	Exon 7 of 18	ENSP00000433624.1	H0YDH6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000678 AC: 1 AN: 147492 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000217 AC: 3 AN: 1382366 Hom.: 0 Cov.: 29 AF XY: 0.00000293 AC XY: 2 AN XY: 682042

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29976

American (AMR) AF: 0.00 AC: 0 AN: 31962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24544

East Asian (EAS) AF: 0.00 AC: 0 AN: 35678

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072720

Other (OTH) AF: 0.0000175 AC: 1 AN: 57184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000468493), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151138 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73756

African (AFR) AF: 0.00 AC: 0 AN: 41272

American (AMR) AF: 0.00 AC: 0 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67530

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.000144 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.49
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.55	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.5	H
PhyloP100		3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.56
gMVP		0.95
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1313458713; hg19: chr6-55940302; COSMIC: COSV55163585; COSMIC: COSV55163585;