NM_001823.5:c.926C>G

Variant names:

• chr14-103520163-G-C
• rs35156510
• NM_001823.5:c.926C>G

Variant summary

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

The NM_001823.5(CKB):​c.926C>G​(p.Ser309Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CKB NM_001823.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

Genes affected

CKB (HGNC:1991): (creatine kinase B) The protein encoded by this gene is a cytoplasmic enzyme involved in energy homeostasis. The encoded protein reversibly catalyzes the transfer of phosphate between ATP and various phosphogens such as creatine phosphate. It acts as a homodimer in brain as well as in other tissues, and as a heterodimer with a similar muscle isozyme in heart. The encoded protein is a member of the ATP:guanido phosphotransferase protein family. A pseudogene of this gene has been characterized. [provided by RefSeq, Jul 2008]

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=0.30600205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKB	NM_001823.5	c.926C>G	p.Ser309Trp	missense_variant	Exon 7 of 8	ENST00000348956.7	NP_001814.2
CKB	NM_001362531.2	c.998C>G	p.Ser333Trp	missense_variant	Exon 6 of 7		NP_001349460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKB	ENST00000348956.7	c.926C>G	p.Ser309Trp	missense_variant	Exon 7 of 8	1	NM_001823.5	ENSP00000299198.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458008 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724984

African (AFR) AF: 0.0000600 AC: 2 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110226

Other (OTH) AF: 0.00 AC: 0 AN: 60212

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.0061
FATHMM_MKL	Benign	0.50	N
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		3.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.074
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0030	D;D
Vest4		0.42
ClinPred		0.93	D
GERP RS		3.7
Varity_R		0.65
gMVP		0.60
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs35156510; hg19: chr14-103986500;