Genetic Variant COL6A5:p.Leu97Ile (chr3-130376458-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001278298.2(COL6A5):c.289C>A(p.Leu97Ile) 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 1,459,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict 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. L97F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071385145).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278298.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL6A5	NM_001278298.2	MANE Select	c.289C>A	p.Leu97Ile	missense	Exon 3 of 41	NP_001265227.1	H0Y393
COL6A5	NM_153264.7		c.289C>A	p.Leu97Ile	missense	Exon 3 of 40	NP_694996.5
COL6A5	NR_022012.3		n.627C>A		non_coding_transcript_exon	Exon 3 of 42

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL6A5	ENST00000373157.9	TSL:2 MANE Select	c.289C>A	p.Leu97Ile	missense	Exon 3 of 41	ENSP00000362250.5	H0Y393
COL6A5	ENST00000312481.11	TSL:1	n.289C>A		non_coding_transcript_exon	Exon 3 of 42	ENSP00000309762.7	A8TX70-1
COL6A5	ENST00000512836.6	TSL:2	c.289C>A	p.Leu97Ile	missense	Exon 3 of 40	ENSP00000422898.2	A8TX70-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459962

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

86024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110986

Other (OTH)

AF:

0.00

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.044

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.67

M_CAP

Benign

0.020

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.87

PhyloP100

-0.098

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.040

REVEL

Benign

0.20

Sift

Benign

0.51

Sift4G

Benign

0.25

Vest4

0.24

MutPred

0.56

Gain of MoRF binding (P = 0.086)

MVP

0.21

MPC

0.044

ClinPred

0.18

GERP RS

-0.59

gMVP

0.21

Mutation Taster

=61/39

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over