Genetic Variant NM_001033081.3:c.433C>T (chr1-39901002-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001033081.3(MYCL):c.433C>T(p.Pro145Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000749 in 1,335,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P145A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

MYCL
NM_001033081.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28895834).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033081.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYCL	NM_001033081.3	MANE Select	c.433C>T	p.Pro145Ser	missense	Exon 1 of 2	NP_001028253.1	P12524-1
MYCL	NM_001033082.3		c.523C>T	p.Pro175Ser	missense	Exon 2 of 3	NP_001028254.2	P12524-3
MYCL	NM_005376.5		c.523C>T	p.Pro175Ser	missense	Exon 2 of 2	NP_005367.2	P12524-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYCL	ENST00000372816.3	TSL:2 MANE Select	c.433C>T	p.Pro145Ser	missense	Exon 1 of 2	ENSP00000361903.2	P12524-1
MYCL	ENST00000397332.3	TSL:1	c.523C>T	p.Pro175Ser	missense	Exon 2 of 3	ENSP00000380494.2	P12524-3
MYCL	ENST00000372815.1	TSL:1	c.523C>T	p.Pro175Ser	missense	Exon 2 of 2	ENSP00000361902.1	P12524-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.49e-7

AC:

AN:

1335730

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

653444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28982

American (AMR)

AF:

0.00

AC:

AN:

24274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20326

East Asian (EAS)

AF:

0.00

AC:

AN:

35216

South Asian (SAS)

AF:

0.00

AC:

AN:

69056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4852

European-Non Finnish (NFE)

AF:

9.50e-7

AC:

AN:

1052126

Other (OTH)

AF:

0.00

AC:

AN:

54964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.29

MetaSVM

Uncertain

-0.28

MutationAssessor

Pathogenic

3.0

PhyloP100

2.5

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.14

Sift

Benign

0.12

Sift4G

Benign

0.19

Polyphen

0.90

Vest4

0.26

MutPred

0.38

Loss of catalytic residue at P145 (P = 1e-04)

MVP

0.60

MPC

1.5

ClinPred

0.93

GERP RS

4.1

Varity_R

0.10

gMVP

0.31

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over