17-82249433-G-A

Position:

chr17-82249433-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001893.6(CSNK1D):c.1055C>T(p.Thr352Met) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000665 in 1,534,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

CSNK1D
NM_001893.6 missense, splice_region

Scores

Splicing: ADA: 0.9987

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.30

Variant links:

Genes affected

CSNK1D (HGNC:2452): (casein kinase 1 delta) This gene is a member of the casein kinase I (CKI) gene family whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein may also be involved in the regulation of apoptosis, circadian rhythm, microtubule dynamics, chromosome segregation, and p53-mediated effects on growth. The encoded protein is highly similar to the mouse and rat CK1 delta homologs. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

CSNK1D links:

SLC16A3 (HGNC:10924): (solute carrier family 16 member 3) Lactic acid and pyruvate transport across plasma membranes is catalyzed by members of the proton-linked monocarboxylate transporter (MCT) family, which has been designated solute carrier family-16. Each MCT appears to have slightly different substrate and inhibitor specificities and transport kinetics, which are related to the metabolic requirements of the tissues in which it is found. The MCTs, which include MCT1 (SLC16A1; MIM 600682) and MCT2 (SLC16A7; MIM 603654), are characterized by 12 predicted transmembrane domains (Price et al., 1998 [PubMed 9425115]).[supplied by OMIM, Mar 2008]

SLC16A3 links:

CSNK1D (HGNC:):

CSNK1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.333791).

BS2

High AC in GnomAdExome4 at 99 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1D	NM_001893.6 linkuse as main transcript	c.1055C>T	p.Thr352Met	missense_variant, splice_region_variant	7/9	ENST00000314028.11	NP_001884.2	P48730-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1D	ENST00000314028.11 linkuse as main transcript	c.1055C>T	p.Thr352Met	missense_variant, splice_region_variant	7/9	1	NM_001893.6	ENSP00000324464.6		P48730-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000456

AC:

AN:

131658

Hom.:

AF XY:

0.0000555

AC XY:

AN XY:

72020

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000413

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000716

AC:

AN:

1382580

Hom.:

Cov.:

AF XY:

0.0000718

AC XY:

AN XY:

682446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000842

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:

0.0000845

Gnomad4 OTH exome

AF:

0.0000865

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000684

Hom.:

Bravo

AF:

0.0000378

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

Jun 10, 2024

The c.1055C>T (p.T352M) alteration is located in exon 7 (coding exon 7) of the CSNK1D gene. This alteration results from a C to T substitution at nucleotide position 1055, causing the threonine (T) at amino acid position 352 to be replaced by a methionine (M). 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

0.098

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.40

.;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.90

.;L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.43

.;N;N

REVEL

Benign

0.19

Sift

Benign

0.042

.;D;D

Sift4G

Benign

0.12

T;T;T

Polyphen

0.94, 0.98

.;P;D

Vest4

0.52

MVP

0.46

MPC

1.5

ClinPred

0.20

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.066

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.68

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

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