Genetic Variant MYT1L:c.-1211A>G (chr2-1842071-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000471668.1(MYT1L):c.-1211A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,172 control chromosomes in the GnomAD database, including 20,964 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 0.49 ( 20958 hom., cov: 33)

Exomes 𝑓: 0.52 ( 6 hom. )

Consequence

MYT1L
ENST00000471668.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.195

Publications

5 publications found

Variant links:

Genes affected

MYT1L (HGNC:7623): (myelin transcription factor 1 like) This gene encodes a member of the zinc finger superfamily of transcription factors whose expression, thus far, has been found only in neuronal tissues. The encoded protein belongs to a novel class of cystein-cystein-histidine-cystein zinc finger proteins that function in the developing mammalian central nervous system. Forced expression of this gene in combination with the basic helix-loop-helix transcription factor NeuroD1 and the transcription factors POU class 3 homeobox 2 and achaete-scute family basic helix-loop-helix transcription factor 1 can convert fetal and postnatal human fibroblasts into induced neuronal cells, which are able to generate action potentials. Mutations in this gene have been associated with an autosomal dominant form of cognitive disability and with autism spectrum disorder. Alternative splicing results in multiple variants. [provided by RefSeq, Jul 2017]

MYT1L Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 39
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

MYT1L links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2 link	c.2775-1228A>G		intron_variant	Intron 19 of 24	ENST00000647738.2	NP_001289981.1	Q9UL68-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2 link	c.2775-1228A>G		intron_variant	Intron 19 of 24		NM_001303052.2	ENSP00000497479.2		Q9UL68-1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74770

AN:

152004

Hom.:

20907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.459

GnomAD4 exome

AF:

0.520

AC:

AN:

Hom.:

Cov.:

AF XY:

0.447

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.492

AC:

74870

AN:

152122

Hom.:

20958

Cov.:

AF XY:

0.490

AC XY:

36405

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.774

AC:

32134

AN:

41538

American (AMR)

AF:

0.362

AC:

5529

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1331

AN:

3466

East Asian (EAS)

AF:

0.666

AC:

3433

AN:

5152

South Asian (SAS)

AF:

0.379

AC:

1821

AN:

4808

European-Finnish (FIN)

AF:

0.405

AC:

4282

AN:

10576

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.367

AC:

24928

AN:

67978

Other (OTH)

AF:

0.459

AC:

967

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1784

3568

5353

7137

8921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.406

Hom.:

7379

Bravo

AF:

0.505

Asia WGS

AF:

0.509

AC:

1767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.69

(source)

DANN

Benign

0.38

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over