rs756445035

Variant names:

• chr6-56059206-C-A
• rs756445035
• NM_030820.4:c.2645G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-56059206-C-A
• chr6-56059206-C-G
• chr6-56059206-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030820.4(COL21A1):​c.2645G>T​(p.Gly882Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G882R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: COL21A1 NM_030820.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.23
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

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.2645G>T	p.Gly882Val	missense	Exon 29 of 30	NP_110447.2
	COL21A1	NM_001318751.2		c.2645G>T	p.Gly882Val	missense	Exon 30 of 31	NP_001305680.1	Q96P44-1
	COL21A1	NM_001318752.2		c.2636G>T	p.Gly879Val	missense	Exon 28 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.2645G>T	p.Gly882Val	missense	Exon 29 of 30	ENSP00000244728.5	Q96P44-1
	COL21A1	ENST00000370819.5	TSL:1	c.2636G>T	p.Gly879Val	missense	Exon 28 of 29	ENSP00000359855.1	Q96P44-3
	COL21A1	ENST00000482933.1	TSL:1	n.1197G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000826 AC: 2 AN: 242124 AF XY: 0.0000152

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: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456128 Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 4 AN XY: 724268

African (AFR) AF: 0.00 AC: 0 AN: 33090

American (AMR) AF: 0.00 AC: 0 AN: 43252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25718

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.00 AC: 0 AN: 85134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110290

Other (OTH) AF: 0.00 AC: 0 AN: 60118

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.46
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.63	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		6.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.44		Gain of sheet (P = 0.0101)
MVP		0.72
MPC		0.022
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.83
gMVP		0.96
Mutation Taster		=62/38	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

Other links and lift over

dbSNP: rs756445035; hg19: chr6-55924004;