NM_004535.3:c.*458A>C

Variant names:

• chr20-64240906-A-C
• rs2427625
• NM_004535.3:c.*458A>C

Variant summary

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

The NM_004535.3(MYT1):​c.*458A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 160,026 control chromosomes in the GnomAD database, including 29,697 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 0.58 (28731 hom., cov: 32)
  • Exomes 𝑓: 0.47 (966 hom.)
• Consequence: MYT1 NM_004535.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 9 publications found

Genes affected

MYT1 (HGNC:7622): (myelin transcription factor 1) The protein encoded by this gene is a member of a family of neural specific, zinc finger-containing DNA-binding proteins. The protein binds to the promoter regions of proteolipid proteins of the central nervous system and plays a role in the developing nervous system. [provided by RefSeq, Jul 2008]

MYT1 Gene-Disease associations (from GenCC):

• craniofacial microsomia

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004535.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1	NM_004535.3	MANE Select	c.*458A>C		3_prime_UTR	Exon 23 of 23	NP_004526.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYT1	ENST00000328439.6	TSL:1 MANE Select	c.*458A>C		3_prime_UTR	Exon 23 of 23	ENSP00000327465.1
	MYT1	ENST00000536311.5	TSL:5	c.*458A>C		3_prime_UTR	Exon 23 of 23	ENSP00000442412.1
	MYT1	ENST00000650655.1		c.*458A>C		3_prime_UTR	Exon 25 of 25	ENSP00000498616.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88790 AN: 151944 Hom.: 28679 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.469 AC: 3739 AN: 7964 Hom.: 966 Cov.: 0 AF XY: 0.472 AC XY: 1914 AN XY: 4058

African (AFR) AF: 0.871 AC: 155 AN: 178

American (AMR) AF: 0.348 AC: 395 AN: 1134

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 125 AN: 182

East Asian (EAS) AF: 0.104 AC: 25 AN: 240

South Asian (SAS) AF: 0.629 AC: 297 AN: 472

European-Finnish (FIN) AF: 0.373 AC: 197 AN: 528

Middle Eastern (MID) AF: 0.625 AC: 5 AN: 8

European-Non Finnish (NFE) AF: 0.483 AC: 2316 AN: 4792

Other (OTH) AF: 0.521 AC: 224 AN: 430

GnomAD4 genome AF: 0.585 AC: 88894 AN: 152062 Hom.: 28731 Cov.: 32 AF XY: 0.574 AC XY: 42677 AN XY: 74338

African (AFR) AF: 0.857 AC: 35586 AN: 41506

American (AMR) AF: 0.449 AC: 6865 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2232 AN: 3468

East Asian (EAS) AF: 0.139 AC: 716 AN: 5158

South Asian (SAS) AF: 0.620 AC: 2993 AN: 4826

European-Finnish (FIN) AF: 0.403 AC: 4252 AN: 10556

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34505 AN: 67960

Other (OTH) AF: 0.564 AC: 1186 AN: 2104

Alfa AF: 0.536 Hom.: 29154

Bravo AF: 0.595

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.43
PhyloP100		-0.94
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: rs2427625; hg19: chr20-62872259; COSMIC: COSV60509061;