Genetic Variant GUCD1:p.Glu4Lys (chr22-24554982-C-T) – 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_001284254.2(GUCD1):c.10G>A(p.Glu4Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GUCD1
NM_001284254.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Publications

0 publications found

Variant links:

Genes affected

GUCD1 (HGNC:14237): (guanylyl cyclase domain containing 1)

GUCD1 links:

Genome browser will be placed here

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=0.1477791).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284254.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUCD1	NM_001284254.2	MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	NP_001271183.1	Q96NT3-2
GUCD1	NM_031444.4		c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	NP_113632.2	Q96NT3-1
GUCD1	NM_001284255.2		c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	NP_001271184.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GUCD1	ENST00000435822.6	TSL:1 MANE Select	c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	ENSP00000405985.1	Q96NT3-2
GUCD1	ENST00000621833.4	TSL:1	c.211+633G>A		intron	N/A	ENSP00000479370.1	A0A087WVD9
GUCD1	ENST00000407471.7	TSL:5	c.10G>A	p.Glu4Lys	missense	Exon 1 of 6	ENSP00000386076.3	Q96NT3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1403090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698308

African (AFR)

AF:

0.00

AC:

AN:

28400

American (AMR)

AF:

0.00

AC:

AN:

35514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23788

East Asian (EAS)

AF:

0.00

AC:

AN:

33590

South Asian (SAS)

AF:

0.00

AC:

AN:

81236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5478

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086952

Other (OTH)

AF:

0.00

AC:

AN:

57448

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

0.21

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0062

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

1.4

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.90

REVEL

Benign

0.24

Sift

Uncertain

0.019

Sift4G

Benign

0.40

Polyphen

0.0080

Vest4

0.31

MutPred

0.14

Gain of ubiquitination at E4 (P = 0.0025)

MVP

0.38

MPC

0.26

ClinPred

0.25

GERP RS

1.3

PromoterAI

0.062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.13

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over