Variant 11-57646399-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_145008.3(YPEL4):c.192C>G(p.Asn64Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

YPEL4
NM_145008.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.970

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YPEL4	NM_145008.3 linkuse as main transcript	c.192C>G	p.Asn64Lys	missense_variant	4/5	ENST00000300022.8	NP_659445.1	Q96NS1A0A024R4Y8
YPEL4	NM_001363487.2 linkuse as main transcript	c.192C>G	p.Asn64Lys	missense_variant	5/6		NP_001350416.1
YPEL4	XM_047426531.1 linkuse as main transcript	c.192C>G	p.Asn64Lys	missense_variant	3/4		XP_047282487.1
MIR130AHG	NR_186232.1 linkuse as main transcript	n.298-3899G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YPEL4	ENST00000300022.8 linkuse as main transcript	c.192C>G	p.Asn64Lys	missense_variant	4/5	1	NM_145008.3	ENSP00000300022.3		Q96NS1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

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

Dec 09, 2024

The c.192C>G (p.N64K) alteration is located in exon 4 (coding exon 3) of the YPEL4 gene. This alteration results from a C to G substitution at nucleotide position 192, causing the asparagine (N) at amino acid position 64 to be replaced by a lysine (K). 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

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

D;D;D;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Benign

0.49

LIST_S2

Pathogenic

1.0

.;.;D;.

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Uncertain

0.36

MutationAssessor

Pathogenic

3.9

H;H;H;.

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-5.8

D;D;D;D

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;.

Polyphen

1.0

D;D;D;.

Vest4

0.99

MutPred

0.93

Gain of methylation at N64 (P = 0.0122);Gain of methylation at N64 (P = 0.0122);Gain of methylation at N64 (P = 0.0122);Gain of methylation at N64 (P = 0.0122);

MVP

0.52

MPC

2.4

ClinPred

1.0

GERP RS

5.2

Varity_R

0.85

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.44

Position offset: 6

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over