Variant chr14-74763575-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019589.3(YLPM1):c.86A>C(p.Glu29Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00132 in 1,579,550 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

YLPM1
NM_019589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

Variant links:

Genes affected

YLPM1 (HGNC:17798): (YLP motif containing 1) Enables RNA binding activity. Predicted to be involved in regulation of telomere maintenance. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

YLPM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018819124).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YLPM1	NM_019589.3 link	c.86A>C	p.Glu29Ala	missense_variant	1/21	ENST00000325680.12	NP_062535.2	P49750-4Q8NF45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YLPM1	ENST00000325680.12 link	c.86A>C	p.Glu29Ala	missense_variant	1/21	5	NM_019589.3	ENSP00000324463.7		P49750-4
YLPM1	ENST00000552421.5 link	c.86A>C	p.Glu29Ala	missense_variant	1/20	5		ENSP00000447921.1		F8VU51

Frequencies

GnomAD3 genomes

AF:

0.000836

AC:

127

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000872

AC:

188

AN:

215686

Hom.:

AF XY:

0.000831

AC XY:

100

AN XY:

120304

show subpopulations

Gnomad AFR exome

AF:

0.000182

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000334

Gnomad NFE exome

AF:

0.00144

Gnomad OTH exome

AF:

0.000976

GnomAD4 exome

AF:

0.00137

AC:

1956

AN:

1427564

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

969

AN XY:

707672

show subpopulations

Gnomad4 AFR exome

AF:

0.000229

Gnomad4 AMR exome

AF:

0.00106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000833

Gnomad4 FIN exome

AF:

0.000330

Gnomad4 NFE exome

AF:

0.00164

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.000836

AC:

127

AN:

151986

Hom.:

Cov.:

AF XY:

0.000673

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000759

Hom.:

Bravo

AF:

0.00100

ESP6500AA

AF:

0.000568

AC:

ESP6500EA

AF:

0.000889

AC:

ExAC

AF:

0.000893

AC:

107

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Oct 08, 2024

The c.86A>C (p.E29A) alteration is located in exon 1 (coding exon 1) of the YLPM1 gene. This alteration results from a A to C substitution at nucleotide position 86, causing the glutamic acid (E) at amino acid position 29 to be replaced by an alanine (A). 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

0.24

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.90

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

0.042

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.092

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.40

T;T

Vest4

0.46

MVP

0.043

MPC

0.12

ClinPred

0.22

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.24

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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