Variant chr3-108920461-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005459.4(GUCA1C):c.329A>G(p.Lys110Arg) 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 1,457,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GUCA1C
NM_005459.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.775

Variant links:

Genes affected

GUCA1C (HGNC:4680): (guanylate cyclase activator 1C) Predicted to enable calcium ion binding activity and calcium sensitive guanylate cyclase activator activity. Predicted to be involved in signal transduction. Predicted to be located in photoreceptor disc membrane. [provided by Alliance of Genome Resources, Apr 2022]

GUCA1C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08049059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GUCA1C	NM_005459.4 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	2/4	ENST00000261047.8	NP_005450.3
GUCA1C	NM_001363884.1 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	2/4		NP_001350813.1
GUCA1C	XM_011513334.3 linkuse as main transcript	c.77A>G	p.Lys26Arg	missense_variant	2/4		XP_011511636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1C	ENST00000261047.8 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	2/4	1	NM_005459.4	ENSP00000261047	P1	O95843-1
GUCA1C	ENST00000393963.7 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	2/4	1		ENSP00000377535
GUCA1C	ENST00000471108.1 linkuse as main transcript	c.329A>G	p.Lys110Arg	missense_variant	2/3	2		ENSP00000417761

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457002

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.329A>G (p.K110R) alteration is located in exon 2 (coding exon 2) of the GUCA1C gene. This alteration results from a A to G substitution at nucleotide position 329, causing the lysine (K) at amino acid position 110 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.26

DEOGEN2

Benign

0.016

.;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.080

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.065

.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.41

N;N;N

REVEL

Benign

0.074

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.083

MutPred

0.58

Loss of ubiquitination at K110 (P = 0.0167);Loss of ubiquitination at K110 (P = 0.0167);Loss of ubiquitination at K110 (P = 0.0167);

MVP

0.68

MPC

0.026

ClinPred

0.073

GERP RS

0.90

Varity_R

0.073

gMVP

0.48

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over