20-64212307-C-T

Variant names:

• chr20-64212307-C-T
• rs351881
• NM_004535.3:c.1517+169C>T

Variant summary

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

The NM_004535.3(MYT1):​c.1517+169C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 149,270 control chromosomes in the GnomAD database, including 479 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 0.062 (479 hom., cov: 31)
• Consequence: MYT1 NM_004535.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYT1	NM_004535.3	c.1517+169C>T		intron_variant	Intron 9 of 22	ENST00000328439.6	NP_004526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYT1	ENST00000328439.6	c.1517+169C>T		intron_variant	Intron 9 of 22	1	NM_004535.3	ENSP00000327465.1

Frequencies

GnomAD3 genomes AF: 0.0622 AC: 9271 AN: 149152 Hom.: 478 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0584

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0829

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0621 AC: 9274 AN: 149270 Hom.: 479 Cov.: 31 AF XY: 0.0603 AC XY: 4394 AN XY: 72886

African (AFR) AF: 0.110 AC: 4396 AN: 39788

American (AMR) AF: 0.0532 AC: 804 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.0829 AC: 284 AN: 3426

East Asian (EAS) AF: 0.0180 AC: 92 AN: 5116

South Asian (SAS) AF: 0.0123 AC: 59 AN: 4784

European-Finnish (FIN) AF: 0.0451 AC: 473 AN: 10484

Middle Eastern (MID) AF: 0.124 AC: 36 AN: 290

European-Non Finnish (NFE) AF: 0.0440 AC: 2965 AN: 67320

Other (OTH) AF: 0.0547 AC: 113 AN: 2064

Alfa AF: 0.0204 Hom.: 13

Bravo AF: 0.0732

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.59
DANN	Benign	0.52
PhyloP100		-3.1
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: rs351881; hg19: chr20-62843660;