Variant chr1-39901002-G-C 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.433C>G(p.Pro145Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,335,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

MYCL
NM_001033081.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

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:

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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=0.26114005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYCL	NM_001033081.3 linkuse as main transcript	c.433C>G	p.Pro145Ala	missense_variant	1/2	ENST00000372816.3
MYCL	NM_001033082.3 linkuse as main transcript	c.523C>G	p.Pro175Ala	missense_variant	2/3
MYCL	NM_005376.5 linkuse as main transcript	c.523C>G	p.Pro175Ala	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYCL	ENST00000372816.3 linkuse as main transcript	c.433C>G	p.Pro145Ala	missense_variant	1/2	2	NM_001033081.3	P4	P12524-1
MYCL	ENST00000397332.3 linkuse as main transcript	c.523C>G	p.Pro175Ala	missense_variant	2/3	1		A1	P12524-3
MYCL	ENST00000372815.1 linkuse as main transcript	c.523C>G	p.Pro175Ala	missense_variant	2/2	1			P12524-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

99200

Hom.:

AF XY:

0.00

AC XY:

AN XY:

52130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000140

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1335730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

653444

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000824

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 06, 2021

The c.523C>G (p.P175A) alteration is located in exon 2 (coding exon 2) of the MYCL gene. This alteration results from a C to G substitution at nucleotide position 523, causing the proline (P) at amino acid position 175 to be replaced by an alanine (A). 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

0.052

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

.;D;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.78

T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.0

.;M;.

MutationTaster

Benign

0.96

N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.098

Sift

Benign

0.23

T;T;D

Sift4G

Benign

0.27

T;T;T

Polyphen

0.72

.;P;.

Vest4

0.29

MutPred

0.35

.;Loss of catalytic residue at P145 (P = 0.0024);.;

MVP

0.59

MPC

1.4

ClinPred

0.81

GERP RS

4.1

Varity_R

0.082

gMVP

0.26

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