rs17039365

Variant names:

• chr2-2193467-T-C
• rs17039365
• NM_001303052.2:c.-420-20479A>G

Variant summary

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

The NM_001303052.2(MYT1L):​c.-420-20479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,204 control chromosomes in the GnomAD database, including 2,464 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 0.17 (2464 hom., cov: 32)
• Consequence: MYT1L NM_001303052.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39
• Publications: 4 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1L	NM_001303052.2	MANE Select	c.-420-20479A>G		intron	N/A	NP_001289981.1	Q9UL68-1
	MYT1L	NM_001329844.2		c.-420-20479A>G		intron	N/A	NP_001316773.1	Q9UL68-1
	MYT1L	NM_001329845.1		c.-420-20479A>G		intron	N/A	NP_001316774.1	Q9UL68-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1L	ENST00000647738.2	MANE Select	c.-420-20479A>G		intron	N/A	ENSP00000497479.2	Q9UL68-1
	MYT1L	ENST00000428368.7	TSL:1	c.-420-20479A>G		intron	N/A	ENSP00000396103.3	Q9UL68-1
	MYT1L	ENST00000399161.8	TSL:1	c.-420-20479A>G		intron	N/A	ENSP00000382114.3	Q9UL68-4

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26315 AN: 152086 Hom.: 2448 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0785

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.173 AC: 26371 AN: 152204 Hom.: 2464 Cov.: 32 AF XY: 0.170 AC XY: 12622 AN XY: 74432

African (AFR) AF: 0.256 AC: 10619 AN: 41528

American (AMR) AF: 0.136 AC: 2085 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3472

East Asian (EAS) AF: 0.127 AC: 659 AN: 5174

South Asian (SAS) AF: 0.0785 AC: 378 AN: 4814

European-Finnish (FIN) AF: 0.130 AC: 1383 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10346 AN: 68004

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.157 Hom.: 8373

Bravo AF: 0.180

Asia WGS AF: 0.102 AC: 353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.046
DANN	Benign	0.35
PhyloP100		-3.4
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: rs17039365; hg19: chr2-2197239;