rs6742365

Variant names:

• chr2-1790037-T-C
• rs6742365
• NM_001303052.2:c.*1830A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-1790037-T-C
• chr2-1790037-T-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.*1830A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,110 control chromosomes in the GnomAD database, including 2,566 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 0.18 (2566 hom., cov: 33)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: MYT1L NM_001303052.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• 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=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.*1830A>G		3_prime_UTR_variant	Exon 25 of 25	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.*1830A>G		3_prime_UTR_variant	Exon 25 of 25		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26858 AN: 151986 Hom.: 2557 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.177 AC: 26913 AN: 152104 Hom.: 2566 Cov.: 33 AF XY: 0.178 AC XY: 13244 AN XY: 74344

African (AFR) AF: 0.250 AC: 10380 AN: 41500

American (AMR) AF: 0.133 AC: 2026 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 527 AN: 3468

East Asian (EAS) AF: 0.0841 AC: 435 AN: 5170

South Asian (SAS) AF: 0.180 AC: 867 AN: 4812

European-Finnish (FIN) AF: 0.179 AC: 1892 AN: 10562

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10231 AN: 68004

Other (OTH) AF: 0.168 AC: 356 AN: 2114

Alfa AF: 0.148 Hom.: 2311

Bravo AF: 0.175

Asia WGS AF: 0.168 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.6
DANN	Benign	0.59
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6742365; hg19: chr2-1793809;