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_36delGAGGAG​(p.Glu11_Glu12del) variant causes a conservative 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 conservative_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]

ENSG00000290147 (HGNC:56129): (GUCA1ANB-GUCA1A readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GUCA1ANB (GUCA1A neighbor) and GUCA1A (guanylate cyclase activator 1A) genes on chromosome 6. The readthrough transcript encodes the same protein as GUCA1A. [provided by RefSeq, Jul 2020]

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_36delGAGGAG	p.Glu11_Glu12del	conservative_inframe_deletion	1/4	ENST00000372958.2	NP_001371839.1
GUCA1ANB-GUCA1A	NM_000409.5	c.31_36delGAGGAG	p.Glu11_Glu12del	conservative_inframe_deletion	3/6		NP_000400.2
GUCA1ANB-GUCA1A	NM_001319061.2	c.31_36delGAGGAG	p.Glu11_Glu12del	conservative_inframe_deletion	3/6		NP_001305990.1
GUCA1ANB-GUCA1A	NM_001319062.2	c.31_36delGAGGAG	p.Glu11_Glu12del	conservative_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_36delGAGGAG	p.Glu11_Glu12del	conservative_inframe_deletion	1/4	1	NM_001384910.1	ENSP00000362049.1
ENSG00000290147	ENST00000654459.1	c.31_36delGAGGAG	p.Glu11_Glu12del	conservative_inframe_deletion	2/5			ENSP00000499539.1

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;