NM_001303052.2:c.2712-14448T>C

Variant names:

• chr2-1866151-A-G
• rs7592630
• NM_001303052.2:c.2712-14448T>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.2712-14448T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,018 control chromosomes in the GnomAD database, including 19,438 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 0.47 (19438 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.2712-14448T>C		intron_variant	Intron 18 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.2712-14448T>C		intron_variant	Intron 18 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71324 AN: 151900 Hom.: 19401 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.470 AC: 71405 AN: 152018 Hom.: 19438 Cov.: 32 AF XY: 0.466 AC XY: 34629 AN XY: 74296

African (AFR) AF: 0.751 AC: 31117 AN: 41450

American (AMR) AF: 0.317 AC: 4845 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3472

East Asian (EAS) AF: 0.654 AC: 3359 AN: 5138

South Asian (SAS) AF: 0.327 AC: 1577 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4030 AN: 10560

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24263 AN: 67974

Other (OTH) AF: 0.414 AC: 874 AN: 2112

Alfa AF: 0.383 Hom.: 39958

Bravo AF: 0.482

Asia WGS AF: 0.491 AC: 1705 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	0.18
DANN	Benign	0.27
PhyloP100		-1.9
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: rs7592630; hg19: chr2-1869923;