Variant 1-26114546-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_152835.5(PDIK1L):c.238A>G(p.Met80Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PDIK1L
NM_152835.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

PDIK1L (HGNC:18981): (PDLIM1 interacting kinase 1 like) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in meiotic cell cycle. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PDIK1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, PDIK1L

BP4

Computational evidence support a benign effect (MetaRNN=0.12713432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDIK1L	NM_152835.5 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	2/3	ENST00000374269.2
PDIK1L	NM_001243532.2 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	2/3
PDIK1L	NM_001243533.2 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PDIK1L	ENST00000374269.2 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	2/3	1	NM_152835.5	P1
PDIK1L	ENST00000374271.8 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	3/4	1		P1
PDIK1L	ENST00000619836.4 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	2/3	3		P1
PDIK1L	ENST00000444713.5 linkuse as main transcript	c.238A>G	p.Met80Val	missense_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2022

The c.238A>G (p.M80V) alteration is located in exon 2 (coding exon 1) of the PDIK1L gene. This alteration results from a A to G substitution at nucleotide position 238, causing the methionine (M) at amino acid position 80 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.021

T;T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.085

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;.;.

M_CAP

Benign

0.0049

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.070

N;.;N;N

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.54

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.43

MutPred

0.40

Loss of disorder (P = 0.1059);Loss of disorder (P = 0.1059);Loss of disorder (P = 0.1059);Loss of disorder (P = 0.1059);

MVP

0.41

MPC

1.1

ClinPred

0.66

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over