chr17-82249578-C-T

Variant names:

• chr17-82249578-C-T
• rs71375089
• NM_001893.6:c.910G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001893.6(CSNK1D):​c.910G>A​(p.Ala304Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,559,244 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A304A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (4 hom.)
• Consequence: CSNK1D NM_001893.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.66
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059715807).
• BP6: Variant 17-82249578-C-T is Benign according to our data. Variant chr17-82249578-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3239068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 215 AD gene.

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.910G>A	p.Ala304Thr	missense	Exon 7 of 9	NP_001884.2
	CSNK1D	NM_001363749.2		c.910G>A	p.Ala304Thr	missense	Exon 7 of 9	NP_001350678.1	H7BYT1
	CSNK1D	NM_139062.4		c.910G>A	p.Ala304Thr	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.910G>A	p.Ala304Thr	missense	Exon 7 of 9	ENSP00000324464.6	P48730-1
	CSNK1D	ENST00000392334.7	TSL:1	c.910G>A	p.Ala304Thr	missense	Exon 7 of 10	ENSP00000376146.2	P48730-2
	CSNK1D	ENST00000580784.5	TSL:1	n.*482G>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000463906.1	J3QQU8

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 215 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00232

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00132 AC: 218 AN: 164534 AF XY: 0.00112

Gnomad AFR exome AF: 0.000624

Gnomad AMR exome AF: 0.000153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00346

Gnomad NFE exome AF: 0.00242

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00215 AC: 3021 AN: 1406892 Hom.: 4 Cov.: 31 AF XY: 0.00208 AC XY: 1447 AN XY: 695596

African (AFR) AF: 0.000397 AC: 13 AN: 32766

American (AMR) AF: 0.000188 AC: 7 AN: 37178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25260

East Asian (EAS) AF: 0.0000530 AC: 2 AN: 37766

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80266

European-Finnish (FIN) AF: 0.00387 AC: 167 AN: 43178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4124

European-Non Finnish (NFE) AF: 0.00254 AC: 2766 AN: 1087902

Other (OTH) AF: 0.00111 AC: 65 AN: 58452

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96 AN XY: 74498

African (AFR) AF: 0.000505 AC: 21 AN: 41578

American (AMR) AF: 0.0000653 AC: 1 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00232 AC: 158 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00114

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000926 AC: 4

ESP6500EA AF: 0.00260 AC: 22

ExAC AF: 0.00110 AC: 126

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		2.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.11
Sift	Benign	0.22	T
Sift4G	Benign	0.34	T
Polyphen		0.0070	B
Vest4		0.29
MVP		0.43
MPC		1.1
ClinPred		0.015	T
GERP RS		4.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.078
gMVP		0.73
Mutation Taster		=76/24	polymorphism

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: rs71375089; hg19: chr17-80207454;