chr12-90978265-GAAA-G
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_004950.5(EPYC):c.166-6_166-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,340,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 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: 𝑓 0.000052 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0021 ( 0 hom. )
Consequence
EPYC
NM_004950.5 splice_region, intron
NM_004950.5 splice_region, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.603
Genes affected
EPYC (HGNC:3053): (epiphycan) Dermatan sulfate proteoglycan 3 is a member of the small leucine-rich repeat proteoglycan family. This gene is composed of seven exons. It regulates fibrillogenesis by interacting with collagen fibrils and other extracellular matrix proteins. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Variant has high frequency in the AMR (0.00554) population. However there is too low homozygotes in high coverage region: (expected more than 1, got 0).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| EPYC | NM_004950.5 | c.166-6_166-4delTTT | splice_region_variant, intron_variant | Intron 2 of 6 | ENST00000261172.8 | NP_004941.2 | ||
| EPYC | XM_011538008.2 | c.-18-6_-18-4delTTT | splice_region_variant, intron_variant | Intron 1 of 5 | XP_011536310.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| EPYC | ENST00000261172.8 | c.166-6_166-4delTTT | splice_region_variant, intron_variant | Intron 2 of 6 | 1 | NM_004950.5 | ENSP00000261172.3 | |||
| EPYC | ENST00000551767.1 | c.166-6_166-4delTTT | splice_region_variant, intron_variant | Intron 2 of 4 | 3 | ENSP00000448272.1 | ||||
| EPYC | ENST00000550203.1 | n.70-6_70-4delTTT | splice_region_variant, intron_variant | Intron 1 of 2 | 3 |
Frequencies
GnomAD3 genomes 0.0000521 AC: 7AN: 134278Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
7
AN:
134278
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00547 AC: 712AN: 130182 AF XY: 0.00518 show subpopulations
GnomAD2 exomes
AF:
AC:
712
AN:
130182
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00206 AC: 2482AN: 1206118Hom.: 0 AF XY: 0.00214 AC XY: 1286AN XY: 601606 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2482
AN:
1206118
Hom.:
AF XY:
AC XY:
1286
AN XY:
601606
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
36
AN:
25202
American (AMR)
AF:
AC:
154
AN:
24214
Ashkenazi Jewish (ASJ)
AF:
AC:
71
AN:
21258
East Asian (EAS)
AF:
AC:
90
AN:
30960
South Asian (SAS)
AF:
AC:
243
AN:
66394
European-Finnish (FIN)
AF:
AC:
145
AN:
39106
Middle Eastern (MID)
AF:
AC:
11
AN:
3486
European-Non Finnish (NFE)
AF:
AC:
1614
AN:
945584
Other (OTH)
AF:
AC:
118
AN:
49914
⚠️ 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: 0.250
Heterozygous variant carriers
0
349
699
1048
1398
1747
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000521 AC: 7AN: 134278Hom.: 0 Cov.: 0 AF XY: 0.0000465 AC XY: 3AN XY: 64582 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
7
AN:
134278
Hom.:
Cov.:
0
AF XY:
AC XY:
3
AN XY:
64582
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
35712
American (AMR)
AF:
AC:
0
AN:
13398
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3280
East Asian (EAS)
AF:
AC:
0
AN:
4658
South Asian (SAS)
AF:
AC:
0
AN:
4148
European-Finnish (FIN)
AF:
AC:
2
AN:
7600
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
5
AN:
62538
Other (OTH)
AF:
AC:
0
AN:
1802
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.239
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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