dbSNP rs3748989: MYT1L:p.Glu97Glu (chr2-1943196-C-T) – 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.291G>A(p.Glu97Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,551,574 control chromosomes in the GnomAD database, including 9,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1122 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8298 hom. )

Consequence

MYT1L
NM_001303052.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.592

Publications

12 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:

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=-0.61).

BP6

Variant 2-1943196-C-T is Benign according to our data. Variant chr2-1943196-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.592 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 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
MYT1L	NM_001303052.2	MANE Select	c.291G>A	p.Glu97Glu	synonymous	Exon 9 of 25	NP_001289981.1
MYT1L	NM_001329844.2		c.291G>A	p.Glu97Glu	synonymous	Exon 10 of 26	NP_001316773.1
MYT1L	NM_001329845.1		c.291G>A	p.Glu97Glu	synonymous	Exon 9 of 25	NP_001316774.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYT1L	ENST00000647738.2	MANE Select	c.291G>A	p.Glu97Glu	synonymous	Exon 9 of 25	ENSP00000497479.2
MYT1L	ENST00000428368.7	TSL:1	c.291G>A	p.Glu97Glu	synonymous	Exon 10 of 26	ENSP00000396103.3
MYT1L	ENST00000399161.8	TSL:1	c.291G>A	p.Glu97Glu	synonymous	Exon 9 of 25	ENSP00000382114.3

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17208

AN:

151834

Hom.:

1122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0701

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0900

Gnomad OTH

AF:

0.100

GnomAD2 exomes

AF:

0.119

AC:

18339

AN:

154706

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0678

Gnomad EAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0907

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.101

AC:

141877

AN:

1399620

Hom.:

8298

Cov.:

AF XY:

0.100

AC XY:

69378

AN XY:

690346

show subpopulations

African (AFR)

AF:

0.137

AC:

4325

AN:

31614

American (AMR)

AF:

0.113

AC:

4035

AN:

35712

Ashkenazi Jewish (ASJ)

AF:

0.0659

AC:

1660

AN:

25180

East Asian (EAS)

AF:

0.313

AC:

11178

AN:

35762

South Asian (SAS)

AF:

0.109

AC:

8623

AN:

79234

European-Finnish (FIN)

AF:

0.114

AC:

5615

AN:

49418

Middle Eastern (MID)

AF:

0.0863

AC:

492

AN:

5700

European-Non Finnish (NFE)

AF:

0.0922

AC:

99474

AN:

1078912

Other (OTH)

AF:

0.111

AC:

6475

AN:

58088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

6853

13706

20559

27412

34265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3862

7724

11586

15448

19310

<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:

0.113

AC:

17219

AN:

151954

Hom.:

1122

Cov.:

AF XY:

0.115

AC XY:

8514

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.134

AC:

5564

AN:

41418

American (AMR)

AF:

0.105

AC:

1603

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0701

AC:

243

AN:

3468

East Asian (EAS)

AF:

0.320

AC:

1642

AN:

5132

South Asian (SAS)

AF:

0.116

AC:

556

AN:

4800

European-Finnish (FIN)

AF:

0.111

AC:

1176

AN:

10568

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0900

AC:

6116

AN:

67992

Other (OTH)

AF:

0.0990

AC:

209

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

746

1493

2239

2986

3732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.0980

Hom.:

2251

Bravo

AF:

0.116

Asia WGS

AF:

0.193

AC:

668

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jul 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.6

(source)

DANN

Benign

0.35

PhyloP100

0.59

Mutation Taster

=99/1

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over