Variant 19-9966377-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The ENST00000264828.4(COL5A3):c.4719G>A(p.Arg1573=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,610,094 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 45 hom. )

Consequence

COL5A3
ENST00000264828.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.666

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 19-9966377-C-T is Benign according to our data. Variant chr19-9966377-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649277.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.666 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL5A3	NM_015719.4 linkuse as main transcript	c.4719G>A	p.Arg1573=	synonymous_variant	64/67	ENST00000264828.4	NP_056534.2
COL5A3	XM_011528042.3 linkuse as main transcript	c.4716G>A	p.Arg1572=	synonymous_variant	64/67		XP_011526344.1
COL5A3	XM_017026849.2 linkuse as main transcript	c.2382G>A	p.Arg794=	synonymous_variant	37/40		XP_016882338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A3	ENST00000264828.4 linkuse as main transcript	c.4719G>A	p.Arg1573=	synonymous_variant	64/67	1	NM_015719.4	ENSP00000264828	P1

Frequencies

GnomAD3 genomes

AF:

0.00518

AC:

788

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00722

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00580

AC:

1438

AN:

248080

Hom.:

AF XY:

0.00574

AC XY:

770

AN XY:

134062

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00459

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.0258

Gnomad NFE exome

AF:

0.00660

Gnomad OTH exome

AF:

0.00861

GnomAD4 exome

AF:

0.00433

AC:

6306

AN:

1457814

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

3176

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.00440

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.00404

Gnomad4 OTH exome

AF:

0.00415

GnomAD4 genome

AF:

0.00517

AC:

788

AN:

152280

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

422

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.00722

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00573

Hom.:

Bravo

AF:

0.00275

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

COL5A3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over