1-47368537-G-T

Variant names:

• chr1-47368537-G-T
• rs35687416
• NM_016308.3:c.240G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016308.3(CMPK1):​c.240G>T​(p.Gln80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,612,670 control chromosomes in the GnomAD database, including 2,040 homozygotes. 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: 𝑓 0.041 (165 hom., cov: 33)
  • Exomes 𝑓: 0.047 (1875 hom.)
• Consequence: CMPK1 NM_016308.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 19 publications found

Genes affected

CMPK1 (HGNC:18170): (cytidine/uridine monophosphate kinase 1) This gene encodes one of the enzymes required for cellular nucleic acid biosynthesis. This enzyme catalyzes the transfer of a phosphate group from ATP to CMP, UMP, or dCMP, to form the corresponding diphosphate nucleotide. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028252602).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMPK1	NM_016308.3	c.240G>T	p.Gln80His	missense_variant	Exon 2 of 6	ENST00000371873.10	NP_057392.1
CMPK1	NM_001366135.1	c.144G>T	p.Gln48His	missense_variant	Exon 2 of 6		NP_001353064.1
CMPK1	NR_046394.2	n.396G>T		non_coding_transcript_exon_variant	Exon 2 of 5
CMPK1	NM_001136140.2	c.172-4418G>T		intron_variant	Intron 1 of 4		NP_001129612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMPK1	ENST00000371873.10	c.240G>T	p.Gln80His	missense_variant	Exon 2 of 6	1	NM_016308.3	ENSP00000360939.5

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6259 AN: 152150 Hom.: 165 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0602

GnomAD2 exomes AF: 0.0472 AC: 11836 AN: 250650 AF XY: 0.0452

Gnomad AFR exome AF: 0.00943

Gnomad AMR exome AF: 0.0610

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.0657

Gnomad NFE exome AF: 0.0466

Gnomad OTH exome AF: 0.0455

GnomAD4 exome AF: 0.0469 AC: 68476 AN: 1460402 Hom.: 1875 Cov.: 30 AF XY: 0.0455 AC XY: 33039 AN XY: 726504

African (AFR) AF: 0.00784 AC: 262 AN: 33434

American (AMR) AF: 0.0642 AC: 2862 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 381 AN: 26126

East Asian (EAS) AF: 0.0853 AC: 3376 AN: 39596

South Asian (SAS) AF: 0.00688 AC: 592 AN: 86074

European-Finnish (FIN) AF: 0.0634 AC: 3383 AN: 53392

Middle Eastern (MID) AF: 0.0165 AC: 95 AN: 5764

European-Non Finnish (NFE) AF: 0.0491 AC: 54575 AN: 1111112

Other (OTH) AF: 0.0489 AC: 2950 AN: 60328

GnomAD4 genome AF: 0.0411 AC: 6261 AN: 152268 Hom.: 165 Cov.: 33 AF XY: 0.0408 AC XY: 3040 AN XY: 74450

African (AFR) AF: 0.0109 AC: 455 AN: 41560

American (AMR) AF: 0.0605 AC: 924 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3470

East Asian (EAS) AF: 0.113 AC: 586 AN: 5180

South Asian (SAS) AF: 0.00993 AC: 48 AN: 4832

European-Finnish (FIN) AF: 0.0663 AC: 702 AN: 10596

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3297 AN: 68030

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0432 Hom.: 469

Bravo AF: 0.0401

TwinsUK AF: 0.0458 AC: 170

ALSPAC AF: 0.0444 AC: 171

ESP6500AA AF: 0.00976 AC: 43

ESP6500EA AF: 0.0483 AC: 415

ExAC AF: 0.0445 AC: 5399

Asia WGS AF: 0.0470 AC: 163 AN: 3478

EpiCase AF: 0.0426

EpiControl AF: 0.0470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.75	T
PhyloP100		2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Vest4		0.13
MutPred		0.55		Gain of ubiquitination at K75 (P = 0.1621);
MPC		1.8
ClinPred		0.029	T
GERP RS		4.3
gMVP		0.51
Mutation Taster		=83/17	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs35687416; hg19: chr1-47834209; COSMIC: COSV64101669;