rs1359016883

Variant names:

• chr17-82249518-G-A
• rs1359016883
• NM_001893.6:c.970C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001893.6(CSNK1D):​c.970C>T​(p.Arg324Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000934 in 1,392,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: CSNK1D NM_001893.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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]

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]

ENSG00000280407 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK1D	NM_001893.6	c.970C>T	p.Arg324Cys	missense_variant	Exon 7 of 9	ENST00000314028.11	NP_001884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK1D	ENST00000314028.11	c.970C>T	p.Arg324Cys	missense_variant	Exon 7 of 9	1	NM_001893.6	ENSP00000324464.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000706 AC: 1 AN: 141670 Hom.: 0 AF XY: 0.0000131 AC XY: 1 AN XY: 76374

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000912

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000934 AC: 13 AN: 1392376 Hom.: 0 Cov.: 31 AF XY: 0.0000175 AC XY: 12 AN XY: 687048

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000741

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.970C>T (p.R324C) 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 970, causing the arginine (R) at amino acid position 324 to be replaced by a cysteine (C). 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	0.31
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	.;D;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.8	.;L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.0	.;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	.;D;D
Sift4G	Uncertain	0.025	D;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.82
MutPred		0.56		Loss of solvent accessibility (P = 0.0036);Loss of solvent accessibility (P = 0.0036);Loss of solvent accessibility (P = 0.0036);
MVP		0.82
MPC		1.5
ClinPred		0.71	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.73

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

Other links and lift over

dbSNP: rs1359016883; hg19: chr17-80207394;