chr2-1791957-T-G

Position:

• chr2-1791957-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2 PP2 BP4_Strong BP6_Moderate

The NM_001303052.2(MYT1L):​c.3471A>C​(p.Glu1157Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYT1L NM_001303052.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.62

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYT1L. . Gene score misZ 4.7706 (greater than the threshold 3.09). Trascript score misZ 5.5162 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 39, syndromic intellectual disability.
• BP4: Computational evidence support a benign effect (MetaRNN=0.03920442).
• BP6: Variant 2-1791957-T-G is Benign according to our data. Variant chr2-1791957-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3298190.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYT1L	NM_001303052.2	c.3471A>C	p.Glu1157Asp	missense_variant	25/25	ENST00000647738.2	NP_001289981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1L	ENST00000647738.2	c.3471A>C	p.Glu1157Asp	missense_variant	25/25		NM_001303052.2	ENSP00000497479

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.026	T;.;.;.;.;.;.;.;.;.;.;T;T;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.81	T;T;T;.;T;.;T;T;T;T;.;.;.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.039	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.6	N;.;.;.;.;.;.;.;.;.;.;N;N;.;.
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	2.2	.;.;N;.;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.11
Sift	Benign	1.0	.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	1.0	.;.;T;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.0	B;.;B;B;.;B;.;.;.;.;B;B;B;B;.
Vest4		0.054
MutPred		0.34		Loss of helix (P = 0.0033);.;.;.;.;.;.;Loss of helix (P = 0.0033);.;.;.;Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);.;.;
MVP		0.068
MPC		0.85
ClinPred		0.17	T
GERP RS		5.1
Varity_R		0.16
gMVP		0.87

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: rs1043635336; hg19: chr2-1795729;