Genetic Variant MYCT1:p.Pro194Leu (chr6-152722126-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025107.3(MYCT1):c.581C>T(p.Pro194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MYCT1
NM_025107.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

Variant links:

Genes affected

MYCT1 (HGNC:23172): (MYC target 1) Predicted to act upstream of or within hematopoietic stem cell homeostasis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYCT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065900385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYCT1	NM_025107.3 link	c.581C>T	p.Pro194Leu	missense_variant	Exon 2 of 2	ENST00000367245.6	NP_079383.2	Q8N699

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYCT1	ENST00000367245.6 link	c.581C>T	p.Pro194Leu	missense_variant	Exon 2 of 2	1	NM_025107.3	ENSP00000356214.5	Q8N699
MYCT1	ENST00000532295.1 link	c.521C>T	p.Pro174Leu	missense_variant	Exon 2 of 3	3		ENSP00000434396.1	H0YDV5
MYCT1	ENST00000529453.1 link	c.197-637C>T		intron_variant	Intron 1 of 1	3		ENSP00000432612.1	E9PQ55

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251332

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.581C>T (p.P194L) alteration is located in exon 2 (coding exon 2) of the MYCT1 gene. This alteration results from a C to T substitution at nucleotide position 581, causing the proline (P) at amino acid position 194 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.041

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.57

M_CAP

Benign

0.014

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.093

Sift

Benign

0.26

Sift4G

Uncertain

0.024

Polyphen

0.0010

Vest4

0.062

MutPred

0.15

Gain of sheet (P = 0.0266);

MVP

0.25

MPC

0.016

ClinPred

0.072

GERP RS

4.9

Varity_R

0.079

gMVP

0.19

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