Variant 12-90972979-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004950.5(EPYC):c.342C>G(p.Asp114Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,566,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

EPYC
NM_004950.5 missense, splice_region

Scores

Splicing: ADA: 0.007802

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09804499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPYC	NM_004950.5 linkuse as main transcript	c.342C>G	p.Asp114Glu	missense_variant, splice_region_variant	4/7	ENST00000261172.8	NP_004941.2
EPYC	XM_011538008.2 linkuse as main transcript	c.159C>G	p.Asp53Glu	missense_variant, splice_region_variant	3/6		XP_011536310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EPYC	ENST00000261172.8 linkuse as main transcript	c.342C>G	p.Asp114Glu	missense_variant, splice_region_variant	4/7	1	NM_004950.5	ENSP00000261172	P1
EPYC	ENST00000551767.1 linkuse as main transcript	c.342C>G	p.Asp114Glu	missense_variant, splice_region_variant	4/5	3		ENSP00000448272
EPYC	ENST00000550203.1 linkuse as main transcript	n.246C>G		splice_region_variant, non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000656

AC:

AN:

228536

Hom.:

AF XY:

0.0000805

AC XY:

AN XY:

124164

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:

0.000131

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.000142

AC:

201

AN:

1414044

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

703206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000314

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:

0.0000193

Gnomad4 NFE exome

AF:

0.000180

Gnomad4 OTH exome

AF:

0.0000687

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.342C>G (p.D114E) alteration is located in exon 4 (coding exon 3) of the EPYC gene. This alteration results from a C to G substitution at nucleotide position 342, causing the aspartic acid (D) at amino acid position 114 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.65

N;.

MutationTaster

Benign

0.90

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.063

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.021

B;.

Vest4

0.31

MutPred

0.34

Gain of catalytic residue at L119 (P = 3e-04);Gain of catalytic residue at L119 (P = 3e-04);

MVP

0.78

MPC

0.017

ClinPred

0.16

GERP RS

3.9

Varity_R

0.15

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0078

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over