16-2973604-A-G

Position:

• chr16-2973604-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004203.5(PKMYT1):​c.1311-389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 506,116 control chromosomes in the GnomAD database, including 42,290 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 0.42 (13866 hom., cov: 32)
  • Exomes 𝑓: 0.39 (28424 hom.)
• Consequence: PKMYT1 NM_004203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

PKMYT1 (HGNC:29650): (protein kinase, membrane associated tyrosine/threonine 1) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein is a membrane-associated kinase that negatively regulates the G2/M transition of the cell cycle by phosphorylating and inactivating cyclin-dependent kinase 1. The activity of the encoded protein is regulated by polo-like kinase 1. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKMYT1	NM_004203.5	c.1311-389T>C		intron_variant		ENST00000262300.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKMYT1	ENST00000262300.13	c.1311-389T>C		intron_variant		1	NM_004203.5

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63721 AN: 151804 Hom.: 13858 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.391 AC: 138474 AN: 354192 Hom.: 28424 Cov.: 6 AF XY: 0.383 AC XY: 70562 AN XY: 184430

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.409

Gnomad4 NFE exome AF: 0.428

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.420 AC: 63755 AN: 151924 Hom.: 13866 Cov.: 32 AF XY: 0.415 AC XY: 30770 AN XY: 74222

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.374

Alfa AF: 0.411 Hom.: 24377

Bravo AF: 0.425

Asia WGS AF: 0.208 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.81

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: rs886427; hg19: chr16-3023605;