Variant 11-57646395-C-T 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.196G>A(p.Gly66Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,874 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: 0.0000082 ( 0 hom. )

Consequence

YPEL4
NM_145008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

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=0.20359764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL4	NM_145008.3 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	4/5	ENST00000300022.8	NP_659445.1	Q96NS1A0A024R4Y8
YPEL4	NM_001363487.2 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	5/6		NP_001350416.1
YPEL4	XM_047426531.1 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	3/4		XP_047282487.1
MIR130AHG	NR_186232.1 linkuse as main transcript	n.298-3903C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL4	ENST00000300022.8 linkuse as main transcript	c.196G>A	p.Gly66Ser	missense_variant	4/5	1	NM_145008.3	ENSP00000300022.3		Q96NS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251372

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135872

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Feb 22, 2024

The c.196G>A (p.G66S) alteration is located in exon 4 (coding exon 3) of the YPEL4 gene. This alteration results from a G to A substitution at nucleotide position 196, causing the glycine (G) at amino acid position 66 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.015

T;T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.075

FATHMM_MKL

Benign

0.75

LIST_S2

Pathogenic

0.99

.;.;D;.

M_CAP

Benign

0.0074

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.77

N;N;N;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.92

T;T;T;T

Sift4G

Benign

0.93

T;T;T;.

Polyphen

0.020

B;B;B;.

Vest4

0.88

MutPred

0.23

Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);

MVP

0.22

MPC

1.3

ClinPred

0.36

GERP RS

5.2

Varity_R

0.30

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

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