rs2050939564

Variant names:

• chr17-82249445-G-C
• rs2050939564
• NM_001893.6:c.1043C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001893.6(CSNK1D):​c.1043C>G​(p.Pro348Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CSNK1D NM_001893.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.71
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3685289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001893.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1D	NM_001893.6	MANE Select	c.1043C>G	p.Pro348Arg	missense	Exon 7 of 9	NP_001884.2
	CSNK1D	NM_001363749.2		c.1043C>G	p.Pro348Arg	missense	Exon 7 of 9	NP_001350678.1	H7BYT1
	CSNK1D	NM_139062.4		c.1043C>G	p.Pro348Arg	missense	Exon 7 of 10	NP_620693.1	P48730-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1D	ENST00000314028.11	TSL:1 MANE Select	c.1043C>G	p.Pro348Arg	missense	Exon 7 of 9	ENSP00000324464.6	P48730-1
	CSNK1D	ENST00000392334.7	TSL:1	c.1043C>G	p.Pro348Arg	missense	Exon 7 of 10	ENSP00000376146.2	P48730-2
	CSNK1D	ENST00000580784.5	TSL:1	n.*615C>G		non_coding_transcript_exon	Exon 3 of 6	ENSP00000463906.1	J3QQU8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385816 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683946

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25120

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1078090

Other (OTH) AF: 0.00 AC: 0 AN: 57852

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		9.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.29
Sift	Benign	0.83	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.67
MutPred		0.23		Gain of MoRF binding (P = 0.0092)
MVP		0.78
MPC		1.2
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.55
Mutation Taster		=41/59	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2050939564; hg19: chr17-80207321;