Variant 6-21065218-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017774.3(CDKAL1):c.1226C>T(p.Pro409Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0518 in 1,604,816 control chromosomes in the GnomAD database, including 2,680 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 0.057 ( 292 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2388 hom. )

Consequence

CDKAL1
NM_017774.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.66

Variant links:

Genes affected

CDKAL1 (HGNC:21050): (CDK5 regulatory subunit associated protein 1 like 1) The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

CDKAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021731853).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKAL1	NM_017774.3 link	c.1226C>T	p.Pro409Leu	missense_variant	12/16	ENST00000274695.8	NP_060244.2	Q5VV42-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKAL1	ENST00000274695.8 link	c.1226C>T	p.Pro409Leu	missense_variant	12/16	1	NM_017774.3	ENSP00000274695.4		Q5VV42-1
CDKAL1	ENST00000378610.1 link	c.1226C>T	p.Pro409Leu	missense_variant	10/14	2		ENSP00000367873.1		Q5VV42-1

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

8700

AN:

152078

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0659

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0901

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0646

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0433

Gnomad OTH

AF:

0.0588

GnomAD3 exomes

AF:

0.0642

AC:

15661

AN:

244014

Hom.:

715

AF XY:

0.0661

AC XY:

8721

AN XY:

131900

show subpopulations

Gnomad AFR exome

AF:

0.0644

Gnomad AMR exome

AF:

0.0391

Gnomad ASJ exome

AF:

0.0956

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0594

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0607

GnomAD4 exome

AF:

0.0512

AC:

74352

AN:

1452620

Hom.:

2388

Cov.:

AF XY:

0.0527

AC XY:

38046

AN XY:

721826

show subpopulations

Gnomad4 AFR exome

AF:

0.0691

Gnomad4 AMR exome

AF:

0.0401

Gnomad4 ASJ exome

AF:

0.0946

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0560

Gnomad4 NFE exome

AF:

0.0427

Gnomad4 OTH exome

AF:

0.0584

GnomAD4 genome

AF:

0.0572

AC:

8701

AN:

152196

Hom.:

292

Cov.:

AF XY:

0.0597

AC XY:

4438

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0659

Gnomad4 AMR

AF:

0.0406

Gnomad4 ASJ

AF:

0.0901

Gnomad4 EAS

AF:

0.147

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0646

Gnomad4 NFE

AF:

0.0432

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0529

Hom.:

398

Bravo

AF:

0.0560

TwinsUK

AF:

0.0418

AC:

155

ALSPAC

AF:

0.0376

AC:

145

ESP6500AA

AF:

0.0604

AC:

266

ESP6500EA

AF:

0.0448

AC:

385

ExAC

AF:

0.0654

AC:

7947

Asia WGS

AF:

0.107

AC:

373

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

D;D

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

D;.

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.8

H;H

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-9.0

D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.20

B;B

Vest4

0.25

MPC

0.36

ClinPred

0.12

GERP RS

5.5

Varity_R

0.60

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over