rs10638570

Positions:

• chr2-1968285-C-CAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001303052.2(MYT1L):​c.152+10879_152+10880insCT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (18955 hom., cov: 0)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.152+10879_152+10880insCT		intron_variant		ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.152+10879_152+10880insCT		intron_variant			NM_001303052.2	ENSP00000497479

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71109 AN: 151898 Hom.: 18907 Cov.: 0

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.468 AC: 71204 AN: 152016 Hom.: 18955 Cov.: 0 AF XY: 0.461 AC XY: 34262 AN XY: 74308

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.420

Alfa AF: 0.430 Hom.: 1668

Asia WGS AF: 0.436 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10638570; hg19: chr2-1972057;