rs17039288

Variant names:

• chr2-2054005-C-T
• rs17039288
• NM_001303052.2:c.-185G>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.-185G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 152,324 control chromosomes in the GnomAD database, including 128 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 0.023 (128 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYT1L NM_001303052.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303052.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1L	NM_001303052.2	MANE Select	c.-185G>A		5_prime_UTR	Exon 4 of 25	NP_001289981.1
	MYT1L	NM_001329844.2		c.-185G>A		5_prime_UTR	Exon 5 of 26	NP_001316773.1
	MYT1L	NM_001329845.1		c.-185G>A		5_prime_UTR	Exon 4 of 25	NP_001316774.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1L	ENST00000647738.2	MANE Select	c.-185G>A		5_prime_UTR	Exon 4 of 25	ENSP00000497479.2
	MYT1L	ENST00000428368.7	TSL:1	c.-185G>A		5_prime_UTR	Exon 5 of 26	ENSP00000396103.3
	MYT1L	ENST00000399161.8	TSL:1	c.-185G>A		5_prime_UTR	Exon 4 of 25	ENSP00000382114.3

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3514 AN: 152206 Hom.: 127 Cov.: 33

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00365

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.0167

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 436 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0231 AC: 3522 AN: 152324 Hom.: 128 Cov.: 33 AF XY: 0.0215 AC XY: 1605 AN XY: 74494

African (AFR) AF: 0.0767 AC: 3188 AN: 41564

American (AMR) AF: 0.00666 AC: 102 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3472

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5188

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00144 AC: 98 AN: 68024

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0101 Hom.: 42

Bravo AF: 0.0259

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.91
Mutation Taster		=300/0	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: rs17039288; hg19: chr2-2057777;