Variant 1-39900980-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033081.3(MYCL):c.455A>C(p.Lys152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,480,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

MYCL
NM_001033081.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.768

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21896741).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCL	NM_001033081.3 linkuse as main transcript	c.455A>C	p.Lys152Thr	missense_variant	1/2	ENST00000372816.3	NP_001028253.1	P12524-1
MYCL	NM_001033082.3 linkuse as main transcript	c.545A>C	p.Lys182Thr	missense_variant	2/3		NP_001028254.2	P12524-3
MYCL	NM_005376.5 linkuse as main transcript	c.545A>C	p.Lys182Thr	missense_variant	2/2		NP_005367.2	P12524-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYCL	ENST00000372816.3 linkuse as main transcript	c.455A>C	p.Lys152Thr	missense_variant	1/2	2	NM_001033081.3	ENSP00000361903.2	P12524-1
MYCL	ENST00000397332.3 linkuse as main transcript	c.545A>C	p.Lys182Thr	missense_variant	2/3	1		ENSP00000380494.2	P12524-3
MYCL	ENST00000372815.1 linkuse as main transcript	c.545A>C	p.Lys182Thr	missense_variant	2/2	1		ENSP00000361902.1	P12524-2

Frequencies

GnomAD3 genomes

AF:

0.0000594

AC:

AN:

151554

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000406

AC:

AN:

98474

Hom.:

AF XY:

0.0000386

AC XY:

AN XY:

51748

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:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000594

AC:

AN:

1329014

Hom.:

Cov.:

AF XY:

0.0000645

AC XY:

AN XY:

651052

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.0000725

Gnomad4 OTH exome

AF:

0.0000552

GnomAD4 genome

AF:

0.0000594

AC:

AN:

151554

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74022

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:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000306

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000294

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

Aug 12, 2024

The c.545A>C (p.K182T) alteration is located in exon 2 (coding exon 2) of the MYCL gene. This alteration results from a A to C substitution at nucleotide position 545, causing the lysine (K) at amino acid position 182 to be replaced by a threonine (T). 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

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.13

T;T;D

Sift4G

Benign

0.078

T;T;D

Polyphen

1.0

.;D;.

Vest4

0.30

MVP

0.66

MPC

1.8

ClinPred

0.31

GERP RS

5.0

Varity_R

0.16

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