Variant 19-45891071-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000322217.6(MYPOP):c.752C>G(p.Pro251Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000285 in 1,490,982 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 0.00014 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

MYPOP
ENST00000322217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.164

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05300519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYPOP	NM_001012643.4 linkuse as main transcript	c.752C>G	p.Pro251Arg	missense_variant	3/3	ENST00000322217.6	NP_001012661.1	Q86VE0
MYPOP	XM_047438749.1 linkuse as main transcript	c.862C>G	p.Pro288Ala	missense_variant	4/4		XP_047294705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYPOP	ENST00000322217.6 linkuse as main transcript	c.752C>G	p.Pro251Arg	missense_variant	3/3	1	NM_001012643.4	ENSP00000325402.4		Q86VE0

Frequencies

GnomAD3 genomes

AF:

0.000140

AC:

AN:

149472

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000741

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:

0.000268

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000960

AC:

AN:

104190

Hom.:

AF XY:

0.0000547

AC XY:

AN XY:

54870

show subpopulations

Gnomad AFR exome

AF:

0.000164

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:

0.000258

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000301

AC:

404

AN:

1341510

Hom.:

Cov.:

AF XY:

0.000284

AC XY:

186

AN XY:

654812

show subpopulations

Gnomad4 AFR exome

AF:

0.0000327

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000253

Gnomad4 NFE exome

AF:

0.000379

Gnomad4 OTH exome

AF:

0.0000717

GnomAD4 genome

AF:

0.000140

AC:

AN:

149472

Hom.:

Cov.:

AF XY:

0.0000961

AC XY:

AN XY:

72860

show subpopulations

Gnomad4 AFR

AF:

0.0000741

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:

0.000268

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.0000324

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

Sep 29, 2023

The c.752C>G (p.P251R) alteration is located in exon 3 (coding exon 2) of the MYPOP gene. This alteration results from a C to G substitution at nucleotide position 752, causing the proline (P) at amino acid position 251 to be replaced by an arginine (R). 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

0.095

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.58

CADD

Benign

3.7

DANN

Benign

0.97

DEOGEN2

Benign

0.0034

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.35

M_CAP

Benign

0.022

MetaRNN

Benign

0.053

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.28

REVEL

Benign

0.043

Sift

Benign

0.40

Sift4G

Benign

0.14

Polyphen

0.36

Vest4

0.11

MutPred

0.20

Loss of glycosylation at P251 (P = 0.0049);

MVP

0.043

MPC

0.25

ClinPred

0.032

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.31

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