Variant 11-57647038-G-A 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_145008.3(YPEL4):c.70C>T(p.Arg24Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,446,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

YPEL4
NM_145008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

YPEL4 (HGNC:18328): (yippee like 4) Predicted to enable metal ion binding activity. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

YPEL4 links:

YPEL4 (HGNC:):

YPEL4 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=0.23300388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL4	NM_145008.3 linkuse as main transcript	c.70C>T	p.Arg24Cys	missense_variant	2/5	ENST00000300022.8	NP_659445.1	Q96NS1A0A024R4Y8
YPEL4	NM_001363487.2 linkuse as main transcript	c.70C>T	p.Arg24Cys	missense_variant	3/6		NP_001350416.1
YPEL4	XM_047426531.1 linkuse as main transcript	c.70C>T	p.Arg24Cys	missense_variant	1/4		XP_047282487.1
MIR130AHG	NR_186232.1 linkuse as main transcript	n.298-3260G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL4	ENST00000300022.8 linkuse as main transcript	c.70C>T	p.Arg24Cys	missense_variant	2/5	1	NM_145008.3	ENSP00000300022.3		Q96NS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000484

AC:

AN:

1446590

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718414

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 22, 2023

The c.70C>T (p.R24C) alteration is located in exon 2 (coding exon 1) of the YPEL4 gene. This alteration results from a C to T substitution at nucleotide position 70, causing the arginine (R) at amino acid position 24 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.039

T;T;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.10

LIST_S2

Pathogenic

0.98

.;.;D;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

N;N;N;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.90

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.031

D;D;D;D

Sift4G

Uncertain

0.037

D;D;D;.

Polyphen

0.98

D;D;D;.

Vest4

0.30

MutPred

0.46

Gain of catalytic residue at P23 (P = 0.0074);Gain of catalytic residue at P23 (P = 0.0074);Gain of catalytic residue at P23 (P = 0.0074);Gain of catalytic residue at P23 (P = 0.0074);

MVP

0.082

MPC

2.4

ClinPred

0.79

GERP RS

4.5

Varity_R

0.13

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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