Genetic Variant NM_001159390.2:c.53C>T (chr1-228140355-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001159390.2(GUK1):c.53C>T(p.Pro18Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,371,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

GUK1
NM_001159390.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.103

Publications

0 publications found

Variant links:

Genes affected

GUK1 (HGNC:4693): (guanylate kinase 1) The protein encoded by this gene is an enzyme that catalyzes the transfer of a phosphate group from ATP to guanosine monophosphate (GMP) to form guanosine diphosphate (GDP). The encoded protein is thought to be a good target for cancer chemotherapy. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

GUK1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

GUK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08371687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159390.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUK1	NM_001159390.2	MANE Select	c.53C>T	p.Pro18Leu	missense	Exon 1 of 8	NP_001152862.1	Q16774-2
GUK1	NM_001242840.3		c.53C>T	p.Pro18Leu	missense	Exon 1 of 7	NP_001229769.1	Q16774-3
GUK1	NM_000858.7		c.-176C>T		5_prime_UTR	Exon 1 of 9	NP_000849.1	Q6IBG8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUK1	ENST00000453943.6	TSL:1 MANE Select	c.53C>T	p.Pro18Leu	missense	Exon 1 of 8	ENSP00000401832.2	B1ANH0
GUK1	ENST00000312726.9	TSL:1	n.53C>T		non_coding_transcript_exon	Exon 1 of 9	ENSP00000317659.5	A0A9L9PY36
GUK1	ENST00000885285.1		c.53C>T	p.Pro18Leu	missense	Exon 1 of 8	ENSP00000555344.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000817

AC:

AN:

122468

AF XY:

0.0000145

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1371434

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

677908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29188

American (AMR)

AF:

0.00

AC:

AN:

32340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23856

East Asian (EAS)

AF:

0.000721

AC:

AN:

34690

South Asian (SAS)

AF:

0.00

AC:

AN:

77980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4868

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075792

Other (OTH)

AF:

0.00

AC:

AN:

57126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.1

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0059

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.57

M_CAP

Benign

0.025

MetaRNN

Benign

0.084

MetaSVM

Benign

-1.0

PhyloP100

-0.10

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.11

REVEL

Benign

0.014

Sift

Benign

0.10

Sift4G

Uncertain

0.040

Vest4

0.075

MutPred

0.29

Loss of loop (P = 0.0112)

MVP

0.24

MPC

0.30

ClinPred

0.13

GERP RS

-0.94

PromoterAI

0.081

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

gMVP

0.48

Mutation Taster

=93/7

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over