3-130379592-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001278298.2(COL6A5):ā€‹c.842A>Gā€‹(p.Asn281Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.981
Variant links:
Genes affected
COL6A5 (HGNC:26674): (collagen type VI alpha 5 chain) This gene encodes a member of the collagen superfamily of proteins. The encoded protein contains multiple von Willebrand factor A-like domains and may interact with the alpha 1 and alpha 2 chains of collagen VI to form the complete collagen VI trimer. Polymorphisms in this gene may be linked to dermal phenotypes, such as eczema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.060977012).
BP6
Variant 3-130379592-A-G is Benign according to our data. Variant chr3-130379592-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3147741.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL6A5NM_001278298.2 linkuse as main transcriptc.842A>G p.Asn281Ser missense_variant 4/41 ENST00000373157.9 NP_001265227.1
COL6A5NM_153264.7 linkuse as main transcriptc.842A>G p.Asn281Ser missense_variant 4/40 NP_694996.5
COL6A5NR_022012.3 linkuse as main transcriptn.1180A>G non_coding_transcript_exon_variant 4/42

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL6A5ENST00000373157.9 linkuse as main transcriptc.842A>G p.Asn281Ser missense_variant 4/412 NM_001278298.2 ENSP00000362250 P2
COL6A5ENST00000312481.11 linkuse as main transcriptc.842A>G p.Asn281Ser missense_variant, NMD_transcript_variant 4/421 ENSP00000309762 A8TX70-1
COL6A5ENST00000512836.6 linkuse as main transcriptc.842A>G p.Asn281Ser missense_variant 4/402 ENSP00000422898 A2A8TX70-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000650
AC:
1
AN:
153834
Hom.:
0
AF XY:
0.0000123
AC XY:
1
AN XY:
81618
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000168
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399212
Hom.:
0
Cov.:
32
AF XY:
0.00000145
AC XY:
1
AN XY:
690120
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 04, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.54
DANN
Benign
0.32
DEOGEN2
Benign
0.10
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.082
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.15
Sift
Benign
0.17
T
Sift4G
Uncertain
0.010
D
Vest4
0.063
MutPred
0.45
Gain of phosphorylation at N281 (P = 0.0357);
MVP
0.18
MPC
0.028
ClinPred
0.069
T
GERP RS
-2.6
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1167029734; hg19: chr3-130098435; API