Genetic Variant GUK1:p.Pro18Gln (chr1-228140355-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001159390.2(GUK1):c.53C>A(p.Pro18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GUK1
NM_001159390.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08752403).

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>A	p.Pro18Gln	missense	Exon 1 of 8	NP_001152862.1	Q16774-2
GUK1	NM_001242840.3		c.53C>A	p.Pro18Gln	missense	Exon 1 of 7	NP_001229769.1	Q16774-3
GUK1	NM_000858.7		c.-176C>A		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>A	p.Pro18Gln	missense	Exon 1 of 8	ENSP00000401832.2	B1ANH0
GUK1	ENST00000312726.9	TSL:1	n.53C>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000317659.5	A0A9L9PY36
GUK1	ENST00000885285.1		c.53C>A	p.Pro18Gln	missense	Exon 1 of 8	ENSP00000555344.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1371432

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677906

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:

0.00

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:

57124

GnomAD4 genome

Cov.:

Alfa

AF:

0.000349

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.1

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0092

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.54

M_CAP

Benign

0.019

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

PhyloP100

-0.10

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.34

REVEL

Benign

0.0070

Sift

Benign

0.10

Sift4G

Uncertain

0.038

Vest4

0.21

MVP

0.15

MPC

0.28

ClinPred

0.11

GERP RS

-0.94

PromoterAI

0.14

Neutral

(source)

gMVP

0.50

Mutation Taster

=92/8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over