rs3748988

Variant names:

• chr2-1943142-A-C
• rs3748988
• NM_001303052.2:c.345T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-1943142-A-C
• chr2-1943142-A-G
• chr2-1943142-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001303052.2(MYT1L):​c.345T>G​(p.Asp115Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D115D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 27)
• Consequence: MYT1L NM_001303052.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 16 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022448063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.345T>G	p.Asp115Glu	missense_variant	Exon 9 of 25	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.345T>G	p.Asp115Glu	missense_variant	Exon 9 of 25		NM_001303052.2	ENSP00000497479.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 17313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0010
DANN	Benign	0.27
DEOGEN2	Benign	0.011	.;T;.;.;.;.;.;.;.;.;.;.;.;.;T;.;T;.;.;.;.;.;.
Eigen	Benign	-2.8
Eigen_PC	Benign	-2.8
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.45	T;T;T;T;.;.;.;T;T;T;T;T;T;.;.;T;.;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.022	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.070	.;N;.;.;N;.;N;.;.;.;.;.;.;N;N;.;N;N;.;.;.;.;.
PhyloP100		-1.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.63	.;.;.;.;N;.;.;.;.;.;.;.;.;.;.;.;N;.;.;.;.;.;.
REVEL	Benign	0.033
Sift	Benign	0.50	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;.
Sift4G	Benign	1.0	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;.
Polyphen		0.0	.;B;.;.;B;.;B;.;.;.;.;.;.;B;B;.;B;B;.;.;.;.;.
Vest4		0.043, 0.044
MutPred		0.27		Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);.;.;Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);Gain of solvent accessibility (P = 0.2601);
MVP		0.12
MPC		0.49
ClinPred		0.054	T
GERP RS		-11
Varity_R		0.035
gMVP		0.0045
Mutation Taster		=88/12	polymorphism

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: rs3748988; hg19: chr2-1946914;