chr6-42173633-G-C

Position:

• chr6-42173633-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001384910.1(GUCA1A):​c.20G>C​(p.Gly7Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GUCA1A NM_001384910.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

Genes affected

GUCA1A (HGNC:4678): (guanylate cyclase activator 1A) This gene encodes an enzyme that plays a role in the recovery of retinal photoreceptors from photobleaching. This enzyme promotes the activity of retinal guanylyl cyclase-1 (GC1) at low calcium concentrations and inhibits GC1 at high calcium concentrations. Mutations in this gene can cause cone dystrophy 3 and code-rod dystrophy 14. provided by RefSeq, Jul 2020]

GUCA1ANB-GUCA1A (HGNC:):

ACMG classification

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=0.273776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCA1A	NM_001384910.1	c.20G>C	p.Gly7Ala	missense_variant	1/4	ENST00000372958.2
GUCA1ANB-GUCA1A	NM_001319061.2	c.20G>C	p.Gly7Ala	missense_variant	3/6
GUCA1ANB-GUCA1A	NM_000409.5	c.20G>C	p.Gly7Ala	missense_variant	3/6
GUCA1ANB-GUCA1A	NM_001319062.2	c.20G>C	p.Gly7Ala	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCA1A	ENST00000372958.2	c.20G>C	p.Gly7Ala	missense_variant	1/4	1	NM_001384910.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 7 of the GUCA1A protein (p.Gly7Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GUCA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 2128726). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.19	.;.;T;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	.;T;.;.;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	.;.;L;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;.;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.17	T;.;T;T;T
Sift4G	Benign	0.69	T;T;T;T;T
Polyphen		0.97	.;.;D;D;D
Vest4		0.40, 0.40, 0.40
MutPred		0.13		Loss of loop (P = 0.1258);.;Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);
MVP		0.84
MPC		0.66
ClinPred		0.70	D
GERP RS		6.0
Varity_R		0.16
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-42141371;