Variant 14-74763868-A-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_019589.3(YLPM1):c.379A>C(p.Met127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,539,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

YLPM1
NM_019589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.808

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:

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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=0.098911196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YLPM1	NM_019589.3 linkuse as main transcript	c.379A>C	p.Met127Leu	missense_variant	1/21	ENST00000325680.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YLPM1	ENST00000325680.12 linkuse as main transcript	c.379A>C	p.Met127Leu	missense_variant	1/21	5	NM_019589.3	P2	P49750-4
YLPM1	ENST00000552421.5 linkuse as main transcript	c.379A>C	p.Met127Leu	missense_variant	1/20	5		A2

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

150954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

187966

Hom.:

AF XY:

0.0000201

AC XY:

AN XY:

99620

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:

0.0000340

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000396

AC:

AN:

1388552

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

683518

show subpopulations

Gnomad4 AFR exome

AF:

0.0000644

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000446

Gnomad4 OTH exome

AF:

0.0000700

GnomAD4 genome

AF:

0.0000331

AC:

AN:

150954

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73640

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.0000591

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.00000833

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 30, 2021

The c.379A>C (p.M127L) 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 379, causing the methionine (M) at amino acid position 127 to be replaced by a leucine (L). 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

Benign

-0.15

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Benign

0.85

DEOGEN2

Benign

0.0099

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.68

N;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.41

T;T

Vest4

0.29

MutPred

0.32

Gain of catalytic residue at M127 (P = 0.0169);Gain of catalytic residue at M127 (P = 0.0169);

MVP

0.068

MPC

0.10

ClinPred

0.22

GERP RS

4.8

Varity_R

0.62

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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