Variant 19-45901296-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000322217.6(MYPOP):c.478C>A(p.Arg160Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000165 in 1,452,318 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MYPOP
ENST00000322217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.01

Variant links:

Genes affected

MYPOP (HGNC:20178): (Myb related transcription factor, partner of profilin) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MYPOP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40915152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYPOP	NM_001012643.4 linkuse as main transcript	c.478C>A	p.Arg160Ser	missense_variant	2/3	ENST00000322217.6	NP_001012661.1	Q86VE0
MYPOP	XM_047438749.1 linkuse as main transcript	c.478C>A	p.Arg160Ser	missense_variant	2/4		XP_047294705.1
MYPOP	XM_047438750.1 linkuse as main transcript	c.478C>A	p.Arg160Ser	missense_variant	2/3		XP_047294706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYPOP	ENST00000322217.6 linkuse as main transcript	c.478C>A	p.Arg160Ser	missense_variant	2/3	1	NM_001012643.4	ENSP00000325402.4		Q86VE0

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000565

AC:

AN:

70806

Hom.:

AF XY:

0.0000285

AC XY:

AN XY:

35056

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.0000712

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000171

AC:

222

AN:

1299990

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

101

AN XY:

632298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000156

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000671

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000118

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000240

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:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000136

ExAC

AF:

0.0000677

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

Jul 14, 2022

The c.478C>A (p.R160S) alteration is located in exon 2 (coding exon 1) of the MYPOP gene. This alteration results from a C to A substitution at nucleotide position 478, causing the arginine (R) at amino acid position 160 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

0.18

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.65

M_CAP

Benign

0.045

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.64

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Benign

0.048

Sift4G

Benign

0.45

Polyphen

0.99

Vest4

0.37

MVP

0.42

MPC

2.5

ClinPred

0.41

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.39

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