rs2427625

Positions:

• chr20-64240906-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYT1	NM_004535.3	c.*458A>C		3_prime_UTR_variant	23/23	ENST00000328439.6	NP_004526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYT1	ENST00000328439.6	c.*458A>C		3_prime_UTR_variant	23/23	1	NM_004535.3	ENSP00000327465	P2
MYT1	ENST00000536311.5	c.*458A>C		3_prime_UTR_variant	23/23	5		ENSP00000442412	A2
MYT1	ENST00000650655.1	c.*458A>C		3_prime_UTR_variant	25/25			ENSP00000498616	P2

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

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.629

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.521

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

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.564

Alfa AF: 0.525 Hom.: 21144

Bravo AF: 0.595

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.43

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: rs2427625; hg19: chr20-62872259; COSMIC: COSV60509061;