6-42173642-TGGAGGA-T

Position:

• chr6-42173642-TGGAGGA-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_001384910.1(GUCA1A):​c.31_36del​(p.Glu11_Glu12del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GUCA1A NM_001384910.1 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.86

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001384910.1.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCA1A	NM_001384910.1	c.31_36del	p.Glu11_Glu12del	inframe_deletion	1/4	ENST00000372958.2	NP_001371839.1
GUCA1ANB-GUCA1A	NM_001319061.2	c.31_36del	p.Glu11_Glu12del	inframe_deletion	3/6		NP_001305990.1
GUCA1ANB-GUCA1A	NM_000409.5	c.31_36del	p.Glu11_Glu12del	inframe_deletion	3/6		NP_000400.2
GUCA1ANB-GUCA1A	NM_001319062.2	c.31_36del	p.Glu11_Glu12del	inframe_deletion	2/5		NP_001305991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1A	ENST00000372958.2	c.31_36del	p.Glu11_Glu12del	inframe_deletion	1/4	1	NM_001384910.1	ENSP00000362049	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

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

Eurofins Ntd Llc (ga)

Jan 18, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1554185944; hg19: chr6-42141380;