2-1792367-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001303052.2(MYT1L):c.3374G>A(p.Ser1125Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,609,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
MYT1L
NM_001303052.2 missense
NM_001303052.2 missense
Scores
5
6
8
Clinical Significance
Conservation
PhyloP100: 7.82
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
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). The gene has 23 curated pathogenic missense variants (we use a threshold of 10). The gene has 25 curated benign missense variants. GenCC has associacion of the gene with intellectual disability, autosomal dominant 39, syndromic intellectual disability.
BP4
Computational evidence support a benign effect (MetaRNN=0.18174487).
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152256Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000332 AC: 8AN: 240638Hom.: 0 AF XY: 0.0000383 AC XY: 5AN XY: 130566
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1457254Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 724370
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74376
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;.;.;D;.;D;D;D;D;D;D;.;.;D;.;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.;M;.;M;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.
REVEL
Benign
Sift
Uncertain
.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.
Sift4G
Uncertain
.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Polyphen
0.99, 0.73, 1.0
.;D;.;.;P;D;.;.;D;.;.;.;.;.;.;D;D;.;D;D;.;.
Vest4
0.64
MutPred
0.22
.;Loss of disorder (P = 0.1297);.;.;.;.;Loss of disorder (P = 0.1297);.;.;Loss of disorder (P = 0.1297);.;.;Loss of disorder (P = 0.1297);.;.;.;Loss of disorder (P = 0.1297);Loss of disorder (P = 0.1297);Loss of disorder (P = 0.1297);.;Loss of disorder (P = 0.1297);.;
MVP
0.44
MPC
2.0
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at