rs6727410

Variant names:

• chr2-1978518-C-T
• rs6727410
• NM_001303052.2:c.152+647G>A

Variant summary

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

The NM_001303052.2(MYT1L):​c.152+647G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,058 control chromosomes in the GnomAD database, including 15,290 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 0.40 (15290 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.152+647G>A		intron_variant	Intron 8 of 24	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.152+647G>A		intron_variant	Intron 8 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61088 AN: 151940 Hom.: 15240 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.402 AC: 61193 AN: 152058 Hom.: 15290 Cov.: 32 AF XY: 0.396 AC XY: 29453 AN XY: 74324

African (AFR) AF: 0.715 AC: 29661 AN: 41480

American (AMR) AF: 0.306 AC: 4665 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2224 AN: 5170

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4814

European-Finnish (FIN) AF: 0.224 AC: 2364 AN: 10564

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18321 AN: 67982

Other (OTH) AF: 0.369 AC: 780 AN: 2114

Alfa AF: 0.310 Hom.: 4463

Bravo AF: 0.426

Asia WGS AF: 0.405 AC: 1405 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	0.39
DANN	Benign	0.40
PhyloP100		0.30
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: rs6727410; hg19: chr2-1982290;