rs11127313

Variant names:

• chr2-1844538-A-G
• rs11127313
• NM_001303052.2:c.2775-3695T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303052.2(MYT1L):​c.2775-3695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,994 control chromosomes in the GnomAD database, including 15,644 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 0.44 (15644 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 4 publications found

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

ENSG00000307932 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.2775-3695T>C		intron_variant	Intron 19 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.2775-3695T>C		intron_variant	Intron 19 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66866 AN: 151876 Hom.: 15626 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.440 AC: 66927 AN: 151994 Hom.: 15644 Cov.: 32 AF XY: 0.439 AC XY: 32642 AN XY: 74272

African (AFR) AF: 0.593 AC: 24580 AN: 41466

American (AMR) AF: 0.341 AC: 5209 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3466

East Asian (EAS) AF: 0.674 AC: 3462 AN: 5136

South Asian (SAS) AF: 0.379 AC: 1822 AN: 4812

European-Finnish (FIN) AF: 0.408 AC: 4315 AN: 10568

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24890 AN: 67956

Other (OTH) AF: 0.419 AC: 885 AN: 2114

Alfa AF: 0.381 Hom.: 5910

Bravo AF: 0.445

Asia WGS AF: 0.496 AC: 1723 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	0.27
DANN	Benign	0.15
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11127313; hg19: chr2-1848310;