Variant 9-134815627-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000093.5(COL5A1):c.4066G>T(p.Ala1356Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COL5A1
NM_000093.5 missense, splice_region

Scores

Splicing: ADA: 0.03165

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Variant links:

Genes affected

COL5A1 (HGNC:2209): (collagen type V alpha 1 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. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

COL5A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38350552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL5A1	NM_000093.5 link	c.4066G>T	p.Ala1356Ser	missense_variant, splice_region_variant	51/66	ENST00000371817.8	NP_000084.3	P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1	NM_001278074.1 link	c.4066G>T	p.Ala1356Ser	missense_variant, splice_region_variant	51/66		NP_001265003.1	B2ZZ86Q59EE7
COL5A1	XM_017014266.3 link	c.4066G>T	p.Ala1356Ser	missense_variant, splice_region_variant	51/65		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8 link	c.4066G>T	p.Ala1356Ser	missense_variant, splice_region_variant	51/66	1	NM_000093.5	ENSP00000360882.3		P20908-1
COL5A1	ENST00000371820.4 link	c.4066G>T	p.Ala1356Ser	missense_variant, splice_region_variant	51/66	2		ENSP00000360885.4		P20908-2H7BY82

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248348

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461328

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726908

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.078

T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.0057

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.38

T;T

MetaSVM

Uncertain

-0.11

MutationAssessor

Benign

0.60

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.25

N;.

REVEL

Uncertain

0.39

Sift

Benign

0.74

T;.

Sift4G

Benign

0.89

T;T

Polyphen

0.35

B;.

Vest4

0.40

MutPred

0.30

Gain of phosphorylation at A1356 (P = 0.0019);Gain of phosphorylation at A1356 (P = 0.0019);

MVP

0.56

MPC

0.27

ClinPred

0.83

GERP RS

5.2

Varity_R

0.084

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.032

dbscSNV1_RF

Benign

0.13

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over