Genetic Variant MYT1L:p.Asp115Asp (chr2-1943142-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001303052.2(MYT1L):c.345T>C(p.Asp115Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,531,704 control chromosomes in the GnomAD database, including 112,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 16289 hom., cov: 27)

Exomes 𝑓: 0.37 ( 96639 hom. )

Consequence

MYT1L
NM_001303052.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -1.59

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-1943142-A-G is Benign according to our data. Variant chr2-1943142-A-G is described in ClinVar as [Benign]. Clinvar id is 1174838.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2 link	c.345T>C	p.Asp115Asp	synonymous_variant	Exon 9 of 25	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.345T>C	p.Asp115Asp	synonymous_variant	Exon 9 of 25		NM_001303052.2	ENSP00000497479.2		Q9UL68-1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

66766

AN:

149422

Hom.:

16250

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.370

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.417

GnomAD3 exomes

AF:

0.390

AC:

60127

AN:

154224

Hom.:

12592

AF XY:

0.385

AC XY:

31366

AN XY:

81466

show subpopulations

Gnomad AFR exome

AF:

0.652

Gnomad AMR exome

AF:

0.335

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.637

Gnomad SAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.369

GnomAD4 exome

AF:

0.367

AC:

507688

AN:

1382168

Hom.:

96639

Cov.:

AF XY:

0.366

AC XY:

249711

AN XY:

682880

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.390

GnomAD4 genome

AF:

0.447

AC:

66845

AN:

149536

Hom.:

16289

Cov.:

AF XY:

0.447

AC XY:

32505

AN XY:

72790

show subpopulations

Gnomad4 AFR

AF:

0.650

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.370

Gnomad4 EAS

AF:

0.631

Gnomad4 SAS

AF:

0.369

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.365

Hom.:

13039

Bravo

AF:

0.453

Asia WGS

AF:

0.494

AC:

1714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.066

DANN

Benign

0.21

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