1-11934722-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000302.4(PLOD1):​c.-58G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

PLOD1
NM_000302.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Publications

0 publications found
Variant links:
Genes affected
PLOD1 (HGNC:9081): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) Lysyl hydroxylase is a membrane-bound homodimeric protein localized to the cisternae of the endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VI have deficiencies in lysyl hydroxylase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
PLOD1 Gene-Disease associations (from GenCC):
  • Ehlers-Danlos syndrome, kyphoscoliotic type 1
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, PanelApp Australia, G2P

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLOD1NM_000302.4 linkc.-58G>T 5_prime_UTR_variant Exon 1 of 19 ENST00000196061.5 NP_000293.2 Q02809-1
PLOD1NM_001316320.2 linkc.-58G>T 5_prime_UTR_variant Exon 1 of 20 NP_001303249.1 Q02809-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLOD1ENST00000196061.5 linkc.-58G>T 5_prime_UTR_variant Exon 1 of 19 1 NM_000302.4 ENSP00000196061.4 Q02809-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.37e-7
AC:
1
AN:
1356246
Hom.:
0
Cov.:
31
AF XY:
0.00000149
AC XY:
1
AN XY:
669058
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
27558
American (AMR)
AF:
0.00
AC:
0
AN:
32888
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24058
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31964
South Asian (SAS)
AF:
0.0000131
AC:
1
AN:
76132
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
34800
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4088
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1068214
Other (OTH)
AF:
0.00
AC:
0
AN:
56544
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.25
CADD
Benign
18
DANN
Benign
0.96
PhyloP100
1.5
PromoterAI
-0.090
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs552712043; hg19: chr1-11994779; API