Variant 3-130376417-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278298.2(COL6A5):c.248A>G(p.His83Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,128 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.168

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]

COL6A5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18034312).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL6A5	NM_001278298.2 link	c.248A>G	p.His83Arg	missense_variant	3/41	ENST00000373157.9	NP_001265227.1	A8TX70H0Y393
COL6A5	NM_153264.7 link	c.248A>G	p.His83Arg	missense_variant	3/40		NP_694996.5	A8TX70-2
COL6A5	NR_022012.3 link	n.586A>G		non_coding_transcript_exon_variant	3/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL6A5	ENST00000373157.9 link	c.248A>G	p.His83Arg	missense_variant	3/41	2	NM_001278298.2	ENSP00000362250.5	H0Y393
COL6A5	ENST00000312481.11 link	n.248A>G		non_coding_transcript_exon_variant	3/42	1		ENSP00000309762.7	A8TX70-1
COL6A5	ENST00000512836.6 link	c.248A>G	p.His83Arg	missense_variant	3/40	2		ENSP00000422898.2	A8TX70-2H0Y935

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461128

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726800

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 31, 2024

The c.248A>G (p.H83R) alteration is located in exon 3 (coding exon 2) of the COL6A5 gene. This alteration results from a A to G substitution at nucleotide position 248, causing the histidine (H) at amino acid position 83 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.10

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.82

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.36

Sift4G

Benign

0.072

Vest4

0.046

MutPred

0.46

Gain of methylation at H83 (P = 0.0311);

MVP

0.20

MPC

0.035

ClinPred

0.27

GERP RS

0.64

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over