16-2973604-A-G

Variant names:

• chr16-2973604-A-G
• rs886427
• NM_004203.5:c.1311-389T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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]

PAQR4 (HGNC:26386): (progestin and adipoQ receptor family member 4) Predicted to enable signaling receptor activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKMYT1	NM_004203.5	MANE Select	c.1311-389T>C		intron	N/A	NP_004194.3
	PKMYT1	NM_001438149.1		c.1311-389T>C		intron	N/A	NP_001425078.1
	PKMYT1	NM_001438150.1		c.1311-389T>C		intron	N/A	NP_001425079.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKMYT1	ENST00000262300.13	TSL:1 MANE Select	c.1311-389T>C		intron	N/A	ENSP00000262300.8	Q99640-1
	PKMYT1	ENST00000431515.6	TSL:2	c.1311-389T>C		intron	N/A	ENSP00000392855.2	B4DZM6
	PKMYT1	ENST00000934455.1		c.1485-389T>C		intron	N/A	ENSP00000604514.1

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

African (AFR) AF: 0.501 AC: 4818 AN: 9624

American (AMR) AF: 0.376 AC: 4785 AN: 12716

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 2996 AN: 8548

East Asian (EAS) AF: 0.158 AC: 2409 AN: 15266

South Asian (SAS) AF: 0.260 AC: 10784 AN: 41426

European-Finnish (FIN) AF: 0.409 AC: 5648 AN: 13812

Middle Eastern (MID) AF: 0.326 AC: 441 AN: 1352

European-Non Finnish (NFE) AF: 0.428 AC: 99861 AN: 233566

Other (OTH) AF: 0.376 AC: 6732 AN: 17882

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

African (AFR) AF: 0.497 AC: 20599 AN: 41424

American (AMR) AF: 0.369 AC: 5642 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1223 AN: 3470

East Asian (EAS) AF: 0.161 AC: 829 AN: 5154

South Asian (SAS) AF: 0.243 AC: 1168 AN: 4810

European-Finnish (FIN) AF: 0.413 AC: 4360 AN: 10552

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28524 AN: 67908

Other (OTH) AF: 0.374 AC: 789 AN: 2108

Alfa AF: 0.415 Hom.: 57222

Bravo AF: 0.425

Asia WGS AF: 0.208 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		1.1
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: rs886427; hg19: chr16-3023605;