rs1617213

Positions:

• chr2-2082602-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001303052.2(MYT1L):​c.-303-28479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,038 control chromosomes in the GnomAD database, including 10,900 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 0.34 (10900 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYT1L	NM_001303052.2	c.-303-28479A>G		intron_variant		ENST00000647738.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYT1L	ENST00000647738.2	c.-303-28479A>G		intron_variant			NM_001303052.2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51254 AN: 151920 Hom.: 10867 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.338 AC: 51330 AN: 152038 Hom.: 10900 Cov.: 32 AF XY: 0.329 AC XY: 24438 AN XY: 74320

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.295

Alfa AF: 0.307 Hom.: 1073

Bravo AF: 0.349

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.3
DANN	Benign	0.84

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

Other links and lift over

dbSNP: rs1617213; hg19: chr2-2086374;