17-82255552-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001893.6(CSNK1D):c.213C>T(p.Cys71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,614,008 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0048 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (44 hom.)
• Consequence: CSNK1D NM_001893.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.400

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-82255552-G-A is Benign according to our data. Variant chr17-82255552-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82255552-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.4 with no splicing effect.
• BS2: High AC in GnomAd at 730 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK1D	NM_001893.6	c.213C>T	p.Cys71=	synonymous_variant	3/9	ENST00000314028.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1D	ENST00000314028.11	c.213C>T	p.Cys71=	synonymous_variant	3/9	1	NM_001893.6	A1

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 152102 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.00862

GnomAD3 exomes AF: 0.00536 AC: 1348 AN: 251488 Hom.: 13 AF XY: 0.00520 AC XY: 707 AN XY: 135922

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00697

Gnomad ASJ exome AF: 0.0166

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.000831

Gnomad NFE exome AF: 0.00758

Gnomad OTH exome AF: 0.00619

GnomAD4 exome AF: 0.00650 AC: 9499 AN: 1461788 Hom.: 44 Cov.: 32 AF XY: 0.00636 AC XY: 4628 AN XY: 727190

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00695

Gnomad4 ASJ exome AF: 0.0184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.00729

Gnomad4 OTH exome AF: 0.00712

GnomAD4 genome AF: 0.00478 AC: 728 AN: 152220 Hom.: 5 Cov.: 32 AF XY: 0.00441 AC XY: 328 AN XY: 74412

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00681

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00712 Hom.: 5

Bravo AF: 0.00538

EpiCase AF: 0.00883

EpiControl AF: 0.00901

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	CSNK1D: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	3.1
Dann	Benign	0.81
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11552086; hg19: chr17-80213428; COSMIC: COSV53925479; COSMIC: COSV53925479;