Genetic Variant NM_001303052.2:c.3255T>C (chr2-1801717-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001303052.2(MYT1L):c.3255T>C(p.Asp1085Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 1,610,066 control chromosomes in the GnomAD database, including 2,403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 201 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2202 hom. )

Consequence

MYT1L
NM_001303052.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.216

Publications

13 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYT1L links:

ENSG00000284600 (HGNC:):

ENSG00000284600 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 2-1801717-A-G is Benign according to our data. Variant chr2-1801717-A-G is described in ClinVar as Benign. ClinVar VariationId is 1282563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.216 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303052.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYT1L	NM_001303052.2	MANE Select	c.3255T>C	p.Asp1085Asp	synonymous	Exon 23 of 25	NP_001289981.1	Q9UL68-1
MYT1L	NM_001329844.2		c.3255T>C	p.Asp1085Asp	synonymous	Exon 24 of 26	NP_001316773.1	Q9UL68-1
MYT1L	NM_001329845.1		c.3255T>C	p.Asp1085Asp	synonymous	Exon 23 of 25	NP_001316774.1	Q9UL68-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYT1L	ENST00000647738.2	MANE Select	c.3255T>C	p.Asp1085Asp	synonymous	Exon 23 of 25	ENSP00000497479.2	Q9UL68-1
MYT1L	ENST00000428368.7	TSL:1	c.3255T>C	p.Asp1085Asp	synonymous	Exon 24 of 26	ENSP00000396103.3	Q9UL68-1
MYT1L	ENST00000399161.8	TSL:1	c.3249T>C	p.Asp1083Asp	synonymous	Exon 23 of 25	ENSP00000382114.3	Q9UL68-4

Frequencies

GnomAD3 genomes

AF:

0.0441

AC:

6717

AN:

152174

Hom.:

201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0156

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0498

Gnomad ASJ

AF:

0.0622

Gnomad EAS

AF:

0.0796

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0739

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0476

Gnomad OTH

AF:

0.0388

GnomAD2 exomes

AF:

0.0607

AC:

14962

AN:

246492

AF XY:

0.0625

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.0699

Gnomad ASJ exome

AF:

0.0656

Gnomad EAS exome

AF:

0.0789

Gnomad FIN exome

AF:

0.0774

Gnomad NFE exome

AF:

0.0487

Gnomad OTH exome

AF:

0.0520

GnomAD4 exome

AF:

0.0509

AC:

74212

AN:

1457774

Hom.:

2202

Cov.:

AF XY:

0.0525

AC XY:

38078

AN XY:

724970

show subpopulations

African (AFR)

AF:

0.0184

AC:

614

AN:

33398

American (AMR)

AF:

0.0705

AC:

3119

AN:

44250

Ashkenazi Jewish (ASJ)

AF:

0.0670

AC:

1749

AN:

26088

East Asian (EAS)

AF:

0.0856

AC:

3394

AN:

39658

South Asian (SAS)

AF:

0.0940

AC:

8004

AN:

85180

European-Finnish (FIN)

AF:

0.0730

AC:

3895

AN:

53364

Middle Eastern (MID)

AF:

0.0888

AC:

511

AN:

5756

European-Non Finnish (NFE)

AF:

0.0450

AC:

49913

AN:

1109808

Other (OTH)

AF:

0.0500

AC:

3013

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

3187

6374

9561

12748

15935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1940

3880

5820

7760

9700

<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:

0.0442

AC:

6730

AN:

152292

Hom.:

201

Cov.:

AF XY:

0.0473

AC XY:

3518

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0160

AC:

664

AN:

41562

American (AMR)

AF:

0.0499

AC:

764

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0622

AC:

216

AN:

3472

East Asian (EAS)

AF:

0.0796

AC:

412

AN:

5176

South Asian (SAS)

AF:

0.101

AC:

487

AN:

4824

European-Finnish (FIN)

AF:

0.0739

AC:

784

AN:

10610

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0476

AC:

3240

AN:

68024

Other (OTH)

AF:

0.0379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

326

652

979

1305

1631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0455

Hom.:

280

Bravo

AF:

0.0418

Asia WGS

AF:

0.0780

AC:

271

AN:

3478

EpiCase

AF:

0.0466

EpiControl

AF:

0.0485

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.4

(source)

DANN

Benign

0.50

PhyloP100

0.22

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over