Genetic Variant NM_001278298.2:c.658G>C (chr3-130376827-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001278298.2(COL6A5):c.658G>C(p.Asp220His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,609,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

COL6A5
NM_001278298.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017870873).

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.658G>C	p.Asp220His	missense	Exon 3 of 41	NP_001265227.1	H0Y393
COL6A5	NM_153264.7		c.658G>C	p.Asp220His	missense	Exon 3 of 40	NP_694996.5
COL6A5	NR_022012.3		n.996G>C		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.658G>C	p.Asp220His	missense	Exon 3 of 41	ENSP00000362250.5	H0Y393
COL6A5	ENST00000312481.11	TSL:1	n.658G>C		non_coding_transcript_exon	Exon 3 of 42	ENSP00000309762.7	A8TX70-1
COL6A5	ENST00000512836.6	TSL:2	c.658G>C	p.Asp220His	missense	Exon 3 of 40	ENSP00000422898.2	A8TX70-2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000704

AC:

AN:

241426

AF XY:

0.0000533

show subpopulations

Gnomad AFR exome

AF:

0.000853

Gnomad AMR exome

AF:

0.0000879

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1457484

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

724688

show subpopulations

African (AFR)

AF:

0.000750

AC:

AN:

33320

American (AMR)

AF:

0.0000675

AC:

AN:

44434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25902

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

85710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109526

Other (OTH)

AF:

0.0000498

AC:

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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

AF:

0.000289

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41558

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.0000830

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.024

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.45

M_CAP

Benign

0.035

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.37

PhyloP100

1.4

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.20

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0010

Vest4

0.13

MVP

0.42

MPC

0.036

ClinPred

0.095

GERP RS

2.5

gMVP

0.39

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over