Variant 19-45890705-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000322217.6(MYPOP):c.1118T>C(p.Leu373Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYPOP
ENST00000322217.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14468032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYPOP	NM_001012643.4 linkuse as main transcript	c.1118T>C	p.Leu373Pro	missense_variant	3/3	ENST00000322217.6	NP_001012661.1	Q86VE0
MYPOP	XM_047438749.1 linkuse as main transcript	c.*256T>C		3_prime_UTR_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.1118T>C	p.Leu373Pro	missense_variant	3/3	1	NM_001012643.4	ENSP00000325402.4		Q86VE0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

74622

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.000917

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000533

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000301

AC:

AN:

165888

Hom.:

AF XY:

0.0000432

AC XY:

AN XY:

92648

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:

0.0000484

Gnomad FIN exome

AF:

0.000120

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000547

AC:

273

AN:

498658

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

131

AN XY:

256940

show subpopulations

Gnomad4 AFR exome

AF:

0.000464

Gnomad4 AMR exome

AF:

0.000129

Gnomad4 ASJ exome

AF:

0.000181

Gnomad4 EAS exome

AF:

0.000113

Gnomad4 SAS exome

AF:

0.000376

Gnomad4 FIN exome

AF:

0.000329

Gnomad4 NFE exome

AF:

0.000647

Gnomad4 OTH exome

AF:

0.000666

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000670

AC:

AN:

74648

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

35178

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000917

Gnomad4 NFE

AF:

0.0000533

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000223

Hom.:

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

Jun 11, 2021

The c.1118T>C (p.L373P) alteration is located in exon 3 (coding exon 2) of the MYPOP gene. This alteration results from a T to C substitution at nucleotide position 1118, causing the leucine (L) at amino acid position 373 to be replaced by a proline (P). 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

0.066

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.32

M_CAP

Benign

0.063

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

REVEL

Benign

0.13

Sift

Uncertain

0.024

Sift4G

Benign

0.26

Polyphen

0.80

Vest4

0.24

MutPred

0.15

Gain of glycosylation at L373 (P = 0.0024);

MVP

0.31

MPC

0.38

ClinPred

0.11

GERP RS

3.1

Varity_R

0.29

gMVP

0.088

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