chr6-56124073-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_030820.4(COL21A1):c.1747C>T(p.Pro583Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000527 in 1,517,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P583R) has been classified as Benign.
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000015 ( 0 hom. )
Consequence
COL21A1
NM_030820.4 missense
NM_030820.4 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 5.42
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]
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ACMG classification
Classification made for transcript
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.1747C>T | p.Pro583Ser | missense_variant | 16/30 | ENST00000244728.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL21A1 | ENST00000244728.10 | c.1747C>T | p.Pro583Ser | missense_variant | 16/30 | 1 | NM_030820.4 | A1 | |
COL21A1 | ENST00000370819.5 | c.1738C>T | p.Pro580Ser | missense_variant | 15/29 | 1 | P4 | ||
COL21A1 | ENST00000488912.5 | c.139C>T | p.Pro47Ser | missense_variant, NMD_transcript_variant | 3/18 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000403 AC: 6AN: 149006Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000146 AC: 2AN: 1368064Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1AN XY: 674176
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GnomAD4 genome AF: 0.0000403 AC: 6AN: 149006Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 2AN XY: 72474
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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 | Jun 30, 2023 | The c.1747C>T (p.P583S) alteration is located in exon 16 (coding exon 15) of the COL21A1 gene. This alteration results from a C to T substitution at nucleotide position 1747, causing the proline (P) at amino acid position 583 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Pathogenic
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
D;.;.
Vest4
MutPred
Gain of phosphorylation at P583 (P = 0.0207);.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at