Variant chr3-108920528-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005459.4(GUCA1C):c.262A>C(p.Lys88Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000279 in 1,436,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GUCA1C
NM_005459.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26438636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GUCA1C	NM_005459.4 linkuse as main transcript	c.262A>C	p.Lys88Gln	missense_variant	2/4	ENST00000261047.8	NP_005450.3
GUCA1C	NM_001363884.1 linkuse as main transcript	c.262A>C	p.Lys88Gln	missense_variant	2/4		NP_001350813.1
GUCA1C	XM_011513334.3 linkuse as main transcript	c.10A>C	p.Lys4Gln	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.262A>C	p.Lys88Gln	missense_variant	2/4	1	NM_005459.4	ENSP00000261047	P1	O95843-1
GUCA1C	ENST00000393963.7 linkuse as main transcript	c.262A>C	p.Lys88Gln	missense_variant	2/4	1		ENSP00000377535
GUCA1C	ENST00000471108.1 linkuse as main transcript	c.262A>C	p.Lys88Gln	missense_variant	2/3	2		ENSP00000417761

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250748

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1436058

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

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 19, 2023

The c.262A>C (p.K88Q) alteration is located in exon 2 (coding exon 2) of the GUCA1C gene. This alteration results from a A to C substitution at nucleotide position 262, causing the lysine (K) at amino acid position 88 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

.;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.1

.;M;.

MutationTaster

Benign

0.80

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.4

N;D;N

REVEL

Benign

0.14

Sift

Uncertain

0.029

D;D;D

Sift4G

Benign

0.21

T;T;T

Polyphen

0.98

D;D;.

Vest4

0.28

MutPred

0.38

Gain of catalytic residue at K88 (P = 0.0305);Gain of catalytic residue at K88 (P = 0.0305);Gain of catalytic residue at K88 (P = 0.0305);

MVP

0.56

MPC

0.21

ClinPred

0.71

GERP RS

5.2

Varity_R

0.78

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over