dbSNP rs748249735: MYCL:p.Lys152Thr (chr1-39900980-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

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

Publications

1 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

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.455A>C	p.Lys152Thr	missense	Exon 1 of 2	NP_001028253.1	P12524-1
MYCL	NM_001033082.3		c.545A>C	p.Lys182Thr	missense	Exon 2 of 3	NP_001028254.2	P12524-3
MYCL	NM_005376.5		c.545A>C	p.Lys182Thr	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.455A>C	p.Lys152Thr	missense	Exon 1 of 2	ENSP00000361903.2	P12524-1
MYCL	ENST00000397332.3	TSL:1	c.545A>C	p.Lys182Thr	missense	Exon 2 of 3	ENSP00000380494.2	P12524-3
MYCL	ENST00000372815.1	TSL:1	c.545A>C	p.Lys182Thr	missense	Exon 2 of 2	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

GnomAD2 exomes

AF:

0.0000406

AC:

AN:

98474

AF XY:

0.0000386

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 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

African (AFR)

AF:

0.00

AC:

AN:

28448

American (AMR)

AF:

0.00

AC:

AN:

23676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20298

East Asian (EAS)

AF:

0.00

AC:

AN:

34228

South Asian (SAS)

AF:

0.00

AC:

AN:

69904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4902

European-Non Finnish (NFE)

AF:

0.0000725

AC:

AN:

1048034

Other (OTH)

AF:

0.0000552

AC:

AN:

54324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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

AF:

0.0000594

AC:

AN:

151554

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41328

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67900

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.4

PhyloP100

0.77

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.2

REVEL

Benign

0.22

Sift

Benign

0.13

Sift4G

Benign

0.078

Polyphen

1.0

Vest4

0.30

MVP

0.66

MPC

1.8

ClinPred

0.31

GERP RS

5.0

Varity_R

0.16

gMVP

0.31

Mutation Taster

=18/82

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over