Genetic Variant PKMYT1:c.1311-389T>C (chr16-2973604-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

21 publications found

Variant links:

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]

PKMYT1 links:

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]

PAQR4 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKMYT1	NM_004203.5 link	c.1311-389T>C		intron_variant	Intron 7 of 8	ENST00000262300.13	NP_004194.3	Q99640-1Q0IJ49
PAQR4	NM_152341.5 link	c.*1656A>G		downstream_gene_variant		ENST00000318782.9	NP_689554.2	Q8N4S7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKMYT1	ENST00000262300.13 link	c.1311-389T>C		intron_variant	Intron 7 of 8	1	NM_004203.5	ENSP00000262300.8		Q99640-1
PAQR4	ENST00000318782.9 link	c.*1656A>G		downstream_gene_variant		1	NM_152341.5	ENSP00000321804.8		Q8N4S7-1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63721

AN:

151804

Hom.:

13858

Cov.:

show subpopulations

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.:

AF XY:

0.383

AC XY:

70562

AN XY:

184430

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

4042

8085

12127

16170

20212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1606

3212

4818

6424

8030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.420

AC:

63755

AN:

151924

Hom.:

13866

Cov.:

AF XY:

0.415

AC XY:

30770

AN XY:

74222

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.420

AC:

28524

AN:

67908

Other (OTH)

AF:

0.374

AC:

789

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1876

3752

5628

7504

9380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over