Variant 14-74763959-A-G 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.470A>G(p.Tyr157Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000645 in 1,240,514 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00067 ( 1 hom. )

Consequence

YLPM1
NM_019589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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 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=0.13595963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YLPM1	NM_019589.3 linkuse as main transcript	c.470A>G	p.Tyr157Cys	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 linkuse as main transcript	c.470A>G	p.Tyr157Cys	missense_variant	1/21	5	NM_019589.3	ENSP00000324463.7		P49750-4
YLPM1	ENST00000552421.5 linkuse as main transcript	c.470A>G	p.Tyr157Cys	missense_variant	1/20	5		ENSP00000447921.1		F8VU51

Frequencies

GnomAD3 genomes

AF:

0.000419

AC:

AN:

102580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000331

Gnomad SAS

AF:

0.000365

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000578

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000283

AC:

AN:

194262

Hom.:

AF XY:

0.000269

AC XY:

AN XY:

104192

show subpopulations

Gnomad AFR exome

AF:

0.000236

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000679

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000368

Gnomad OTH exome

AF:

0.000447

GnomAD4 exome

AF:

0.000665

AC:

757

AN:

1137934

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

368

AN XY:

558394

show subpopulations

Gnomad4 AFR exome

AF:

0.000205

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.0000714

Gnomad4 EAS exome

AF:

0.000414

Gnomad4 SAS exome

AF:

0.0000839

Gnomad4 FIN exome

AF:

0.0000306

Gnomad4 NFE exome

AF:

0.000793

Gnomad4 OTH exome

AF:

0.000435

GnomAD4 genome

AF:

0.000419

AC:

AN:

102580

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

AN XY:

46738

show subpopulations

Gnomad4 AFR

AF:

0.000352

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000331

Gnomad4 SAS

AF:

0.000365

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000578

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000386

Hom.:

ESP6500AA

AF:

0.000509

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000257

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

Nov 19, 2022

The c.470A>G (p.Y157C) alteration is located in exon 1 (coding exon 1) of the YLPM1 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the tyrosine (Y) at amino acid position 157 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

0.19

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.056

T;T

Eigen

Benign

0.19

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.14

T;T

Vest4

0.57

MVP

0.043

MPC

0.14

ClinPred

0.089

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.47

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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