chr21-46001259-A-T

Variant summary

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

Score: 1 - Uncertain Significance
1
-12 -7 -6 -1 0 5 6 9 10 12
PM2BP4

The NM_001848.3(COL6A1):​c.1829A>T​(p.Lys610Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. K610T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

COL6A1
NM_001848.3 missense

Scores

10
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.775

Publications

0 publications found
Variant links:
Genes affected
COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]
COL6A1 Gene-Disease associations (from GenCC):
  • collagen 6-related myopathy
    Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
  • Bethlem myopathy 1A
    Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
  • Ullrich congenital muscular dystrophy 1A
    Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • Bethlem myopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Ullrich congenital muscular dystrophy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.3753069).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL6A1NM_001848.3 linkc.1829A>T p.Lys610Met missense_variant Exon 30 of 35 ENST00000361866.8 NP_001839.2 P12109A0A384P5H7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL6A1ENST00000361866.8 linkc.1829A>T p.Lys610Met missense_variant Exon 30 of 35 1 NM_001848.3 ENSP00000355180.3 P12109

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455630
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724368
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33454
American (AMR)
AF:
0.00
AC:
0
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26118
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39670
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48050
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111352
Other (OTH)
AF:
0.00
AC:
0
AN:
60280
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.75
D;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.38
FATHMM_MKL
Benign
0.0096
N
LIST_S2
Benign
0.85
T;D
M_CAP
Uncertain
0.21
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Uncertain
-0.086
T
MutationAssessor
Benign
1.9
M;.
PhyloP100
0.78
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-2.8
D;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0060
D;.
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.61
P;.
Vest4
0.49
MutPred
0.48
Loss of methylation at K610 (P = 0);.;
MVP
0.62
MPC
0.85
ClinPred
0.93
D
GERP RS
1.3
PromoterAI
-0.070
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.57
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs768906709; hg19: chr21-47421173; API