Genetic Variant EPYC:c.166-8_166-4delTTTTT (chr12-90978265-GAAAAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_004950.5(EPYC):c.166-8_166-4delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,222,900 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

EPYC
NM_004950.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34

Variant links:

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]

EPYC links:

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ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPYC	NM_004950.5 link	c.166-8_166-4delTTTTT		splice_region_variant, intron_variant	Intron 2 of 6	ENST00000261172.8	NP_004941.2	Q99645A0A024RBC3
EPYC	XM_011538008.2 link	c.-18-8_-18-4delTTTTT		splice_region_variant, intron_variant	Intron 1 of 5		XP_011536310.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPYC	ENST00000261172.8 link	c.166-8_166-4delTTTTT	splice_region_variant, intron_variant	Intron 2 of 6	1	NM_004950.5	ENSP00000261172.3	Q99645
EPYC	ENST00000551767.1 link	c.166-8_166-4delTTTTT	splice_region_variant, intron_variant	Intron 2 of 4	3		ENSP00000448272.1	F8VSI4
EPYC	ENST00000550203.1 link	n.70-8_70-4delTTTTT	splice_region_variant, intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000270

AC:

AN:

1222900

Hom.:

AF XY:

0.0000213

AC XY:

AN XY:

610092

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000394

AC:

AN:

25398

American (AMR)

AF:

0.000286

AC:

AN:

24436

Ashkenazi Jewish (ASJ)

AF:

0.0000462

AC:

AN:

21646

East Asian (EAS)

AF:

0.000127

AC:

AN:

31494

South Asian (SAS)

AF:

0.0000447

AC:

AN:

67176

European-Finnish (FIN)

AF:

0.0000753

AC:

AN:

39848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3540

European-Non Finnish (NFE)

AF:

0.0000125

AC:

AN:

958644

Other (OTH)

AF:

0.0000394

AC:

AN:

50718

⚠️ 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: 0.249

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Splicing

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

Publications

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chr12-90978265-GAAAAA-G