Variant 14-74763512-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019589.3(YLPM1):c.23A>G(p.Tyr8Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,338,044 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000015 ( 1 hom. )

Consequence

YLPM1
NM_019589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YLPM1	NM_019589.3 linkuse as main transcript	c.23A>G	p.Tyr8Cys	missense_variant	1/21	ENST00000325680.12	NP_062535.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YLPM1	ENST00000325680.12 linkuse as main transcript	c.23A>G	p.Tyr8Cys	missense_variant	1/21	5	NM_019589.3	ENSP00000324463	P2	P49750-4
YLPM1	ENST00000552421.5 linkuse as main transcript	c.23A>G	p.Tyr8Cys	missense_variant	1/20	5		ENSP00000447921	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000207

AC:

AN:

144768

Hom.:

AF XY:

0.0000372

AC XY:

AN XY:

80574

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:

0.000186

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1338044

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

655058

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:

0.000227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000191

Gnomad4 OTH exome

AF:

0.0000367

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000277

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 22, 2022

The c.23A>G (p.Y8C) 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 23, causing the tyrosine (Y) at amino acid position 8 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

0.25

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.026

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

.;L

MutationTaster

Benign

0.52

D;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0030

D;D

Vest4

0.79

MutPred

0.27

Gain of catalytic residue at Y8 (P = 0.0026);Gain of catalytic residue at Y8 (P = 0.0026);

MVP

0.043

MPC

0.14

ClinPred

0.48

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.71

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