2-1842071-T-C

Variant names:

• chr2-1842071-T-C
• rs4073401
• ENST00000471668.1:c.-1211A>G

Variant summary

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

The ENST00000471668.1(MYT1L):​c.-1211A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,172 control chromosomes in the GnomAD database, including 20,964 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 0.49 (20958 hom., cov: 33)
  • Exomes 𝑓: 0.52 (6 hom.)
• Consequence: MYT1L ENST00000471668.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.2775-1228A>G		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.2775-1228A>G		intron_variant	Intron 19 of 24		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74770 AN: 152004 Hom.: 20907 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.520 AC: 26 AN: 50 Hom.: 6 Cov.: 0 AF XY: 0.447 AC XY: 17 AN XY: 38

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.492 AC: 74870 AN: 152122 Hom.: 20958 Cov.: 33 AF XY: 0.490 AC XY: 36405 AN XY: 74354

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.459

Alfa AF: 0.404 Hom.: 6535

Bravo AF: 0.505

Asia WGS AF: 0.509 AC: 1767 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	0.69
DANN	Benign	0.38

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: rs4073401; hg19: chr2-1845843;