Variant rs3134614 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001033081.3(MYCL):c.1085C>G(p.Thr362Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,597,414 control chromosomes in the GnomAD database, including 620,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.91 ( 63209 hom., cov: 33)

Exomes 𝑓: 0.88 ( 557770 hom. )

Consequence

MYCL
NM_001033081.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

MYCL (HGNC:7555): (MYCL proto-oncogene, bHLH transcription factor) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of inner ear auditory receptor cell differentiation. Located in chromosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYCL links:

MYCL-AS1 (HGNC:):

MYCL-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.394342E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCL	NM_001033081.3 linkuse as main transcript	c.1085C>G	p.Thr362Ser	missense_variant	2/2	ENST00000372816.3	NP_001028253.1	P12524-1
MYCL	NM_001033082.3 linkuse as main transcript	c.1175C>G	p.Thr392Ser	missense_variant	3/3		NP_001028254.2	P12524-3
MYCL-AS1	NR_183424.1 linkuse as main transcript	n.273-361G>C		intron_variant
MYCL-AS1	NR_183425.1 linkuse as main transcript	n.36-361G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCL	ENST00000372816.3 linkuse as main transcript	c.1085C>G	p.Thr362Ser	missense_variant	2/2	2	NM_001033081.3	ENSP00000361903.2		P12524-1
MYCL	ENST00000397332.3 linkuse as main transcript	c.1175C>G	p.Thr392Ser	missense_variant	3/3	1		ENSP00000380494.2		P12524-3

Frequencies

GnomAD3 genomes

AF:

0.909

AC:

138378

AN:

152194

Hom.:

63149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.977

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.897

Gnomad ASJ

AF:

0.853

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.832

Gnomad FIN

AF:

0.895

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.875

Gnomad OTH

AF:

0.905

GnomAD3 exomes

AF:

0.885

AC:

217303

AN:

245514

Hom.:

96484

AF XY:

0.879

AC XY:

116669

AN XY:

132662

show subpopulations

Gnomad AFR exome

AF:

0.977

Gnomad AMR exome

AF:

0.872

Gnomad ASJ exome

AF:

0.856

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.826

Gnomad FIN exome

AF:

0.894

Gnomad NFE exome

AF:

0.873

Gnomad OTH exome

AF:

0.885

GnomAD4 exome

AF:

0.878

AC:

1268532

AN:

1445102

Hom.:

557770

Cov.:

AF XY:

0.875

AC XY:

626814

AN XY:

716116

show subpopulations

Gnomad4 AFR exome

AF:

0.980

Gnomad4 AMR exome

AF:

0.876

Gnomad4 ASJ exome

AF:

0.860

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.885

Gnomad4 NFE exome

AF:

0.874

Gnomad4 OTH exome

AF:

0.885

GnomAD4 genome

AF:

0.909

AC:

138499

AN:

152312

Hom.:

63209

Cov.:

AF XY:

0.910

AC XY:

67746

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.977

Gnomad4 AMR

AF:

0.897

Gnomad4 ASJ

AF:

0.853

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.895

Gnomad4 NFE

AF:

0.875

Gnomad4 OTH

AF:

0.906

Alfa

AF:

0.886

Hom.:

16783

Bravo

AF:

0.914

TwinsUK

AF:

0.872

AC:

3234

ALSPAC

AF:

0.880

AC:

3392

ESP6500AA

AF:

0.975

AC:

4295

ESP6500EA

AF:

0.867

AC:

7458

ExAC

AF:

0.884

AC:

107296

Asia WGS

AF:

0.939

AC:

3267

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.23

.;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.19

T;T

MetaRNN

Benign

5.4e-7

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.77

.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.21

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.019

MutPred

0.16

.;Gain of disorder (P = 0.1617);

MPC

0.60

ClinPred

0.0012

GERP RS

4.5

Varity_R

0.048

gMVP

0.086

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over