NM_015719.4:c.4592G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_015719.4(COL5A3):c.4592G>A(p.Arg1531Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,539,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

COL5A3
NM_015719.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.415

Publications

0 publications found

Variant links:

Genes affected

COL5A3 (HGNC:14864): (collagen type V alpha 3 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are thought to be responsible for the symptoms of a subset of patients with Ehlers-Danlos syndrome type III. Messages of several sizes can be detected in northern blots but sequence information cannot confirm the identity of the shorter messages. [provided by RefSeq, Jul 2008]

COL5A3 links:

ENSG00000295554 (HGNC:):

ENSG00000295554 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107668936).

BP6

Variant 19-9966613-C-T is Benign according to our data. Variant chr19-9966613-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 4005463.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015719.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A3	NM_015719.4	MANE Select	c.4592G>A	p.Arg1531Gln	missense	Exon 63 of 67	NP_056534.2	P25940

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A3	ENST00000264828.4	TSL:1 MANE Select	c.4592G>A	p.Arg1531Gln	missense	Exon 63 of 67	ENSP00000264828.3	P25940
	ENSG00000295554	ENST00000730923.1		n.74-17437C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000222

AC:

AN:

135376

AF XY:

0.0000271

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000396

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1387046

Hom.:

Cov.:

AF XY:

0.0000161

AC XY:

AN XY:

684606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31562

American (AMR)

AF:

0.0000280

AC:

AN:

35720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25158

East Asian (EAS)

AF:

0.00

AC:

AN:

35774

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4654

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

1078922

Other (OTH)

AF:

0.00

AC:

AN:

57812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000459

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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:

0.0000327

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000410

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.071

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.78

M_CAP

Benign

0.051

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.6

PhyloP100

-0.41

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

REVEL

Benign

0.18

Sift

Benign

0.058

Sift4G

Uncertain

0.060

Polyphen

0.0030

Vest4

0.072

MutPred

0.49

Loss of glycosylation at P1534 (P = 0.1336)

MVP

0.55

MPC

1.8

ClinPred

0.33

GERP RS

0.036

Varity_R

0.066

gMVP

0.43

Mutation Taster

=95/5

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