rs140797509

Variant names:

• chr9-134814873-C-A
• NM_000093.5:c.3983C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134814873-C-A
• chr9-134814873-C-G
• chr9-134814873-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000093.5(COL5A1):​c.3983C>A​(p.Pro1328His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: COL5A1 NM_000093.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL5A1	NM_000093.5	c.3983C>A	p.Pro1328His	missense_variant	Exon 50 of 66	ENST00000371817.8	NP_000084.3
COL5A1	NM_001278074.1	c.3983C>A	p.Pro1328His	missense_variant	Exon 50 of 66		NP_001265003.1
COL5A1	XM_017014266.3	c.3983C>A	p.Pro1328His	missense_variant	Exon 50 of 65		XP_016869755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL5A1	ENST00000371817.8	c.3983C>A	p.Pro1328His	missense_variant	Exon 50 of 66	1	NM_000093.5	ENSP00000360882.3
COL5A1	ENST00000371820.4	c.3983C>A	p.Pro1328His	missense_variant	Exon 50 of 66	2		ENSP00000360885.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398926 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689986

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.7	L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.1	D;.
REVEL	Pathogenic	0.78
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.050	T;T
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.43		Loss of catalytic residue at P1328 (P = 0.0629);Loss of catalytic residue at P1328 (P = 0.0629);
MVP		0.79
MPC		0.34
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.75
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-137706719;