rs766194518

Variant names:

• chr6-56057820-C-T
• rs766194518
• NM_030820.4:c.2711G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030820.4(COL21A1):​c.2711G>A​(p.Ser904Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000063 in 1,428,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: COL21A1 NM_030820.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.85
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33930707).

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.2711G>A	p.Ser904Asn	missense	Exon 30 of 30	NP_110447.2
	COL21A1	NM_001318751.2		c.2711G>A	p.Ser904Asn	missense	Exon 31 of 31	NP_001305680.1	Q96P44-1
	COL21A1	NM_001318752.2		c.2702G>A	p.Ser901Asn	missense	Exon 29 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.2711G>A	p.Ser904Asn	missense	Exon 30 of 30	ENSP00000244728.5	Q96P44-1
	COL21A1	ENST00000370819.5	TSL:1	c.2702G>A	p.Ser901Asn	missense	Exon 29 of 29	ENSP00000359855.1	Q96P44-3
	COL21A1	ENST00000482933.1	TSL:1	n.1263G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000497 AC: 1 AN: 201058 AF XY: 0.00000915

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: 0.0000111

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000630 AC: 9 AN: 1428852 Hom.: 0 Cov.: 31 AF XY: 0.00000705 AC XY: 5 AN XY: 709418

African (AFR) AF: 0.00 AC: 0 AN: 31698

American (AMR) AF: 0.00 AC: 0 AN: 37744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24912

East Asian (EAS) AF: 0.00 AC: 0 AN: 38194

South Asian (SAS) AF: 0.00 AC: 0 AN: 81674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.00000729 AC: 8 AN: 1097970

Other (OTH) AF: 0.0000170 AC: 1 AN: 58922

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000372 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00000831 AC: 1

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	Benign	0.25
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.5	L
PhyloP100		6.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.58	N
REVEL	Uncertain	0.45
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.97	D
Vest4		0.31
MVP		0.73
MPC		0.019
ClinPred		0.52	D
GERP RS		4.2
Varity_R		0.18
gMVP		0.30
Mutation Taster		=85/15	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: rs766194518; hg19: chr6-55922618;