Variant 8-66566232-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001080416.4(MYBL1):c.1962A>T(p.Arg654Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000289 in 1,471,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

MYBL1
NM_001080416.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.337

Variant links:

Genes affected

MYBL1 (HGNC:7547): (MYB proto-oncogene like 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYBL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032775015).

BS2

High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYBL1	NM_001080416.4 linkuse as main transcript	c.1962A>T	p.Arg654Ser	missense_variant	15/16	ENST00000522677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYBL1	ENST00000522677.8 linkuse as main transcript	c.1962A>T	p.Arg654Ser	missense_variant	15/16	1	NM_001080416.4	A1	P10243-1
MYBL1	ENST00000524176.2 linkuse as main transcript	c.1950+452A>T		intron_variant		1		P4	P10243-2
MYBL1	ENST00000517885.5 linkuse as main transcript	c.936A>T	p.Arg312Ser	missense_variant	11/12	5
MYBL1	ENST00000522419.1 linkuse as main transcript	n.188+452A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

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:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000176

AC:

AN:

130524

Hom.:

AF XY:

0.000145

AC XY:

AN XY:

69064

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:

0.00

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000306

AC:

404

AN:

1319686

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

173

AN XY:

653718

show subpopulations

Gnomad4 AFR exome

AF:

0.000140

Gnomad4 AMR exome

AF:

0.0000367

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000165

Gnomad4 NFE exome

AF:

0.000366

Gnomad4 OTH exome

AF:

0.000290

GnomAD4 genome

AF:

0.000145

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74228

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:

0.000283

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000200

ExAC

AF:

0.000147

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

Feb 22, 2023

The c.1962A>T (p.R654S) alteration is located in exon 15 (coding exon 15) of the MYBL1 gene. This alteration results from a A to T substitution at nucleotide position 1962, causing the arginine (R) at amino acid position 654 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.22

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.61

N;N

REVEL

Benign

0.016

Sift

Benign

0.12

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0

B;.

Vest4

0.078

MutPred

0.42

Gain of disorder (P = 0.0588);.;

MVP

0.068

MPC

0.11

ClinPred

0.077

GERP RS

3.3

Varity_R

0.13

gMVP

0.22

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