Variant 6-42162964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001384994.1(CIMIP3):c.54G>A(p.Pro18Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 699,614 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: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

CIMIP3
NM_001384994.1 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.418

Variant links:

Genes affected

CIMIP3 (HGNC:55126): (ciliary microtubule inner protein 3) Predicted to enable guanylate cyclase regulator activity. Predicted to be involved in positive regulation of guanylate cyclase activity. Predicted to act upstream of or within phototransduction; regulation of guanylate cyclase activity; and visual perception. Predicted to be located in cone photoreceptor outer segment and photoreceptor inner segment. [provided by Alliance of Genome Resources, Apr 2022]

CIMIP3 links:

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]

ENSG00000290147 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-0.418 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIMIP3	NM_001384994.1 link	c.54G>A	p.Pro18Pro	synonymous_variant	2/2	ENST00000623004.2	NP_001371923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCA1ANB	ENST00000623004.2 link	c.54G>A	p.Pro18Pro	synonymous_variant	2/2	3	NM_001384994.1	ENSP00000485219.1		A0A096LNT9
ENSG00000290147	ENST00000654459.1 link	c.-282+7371G>A		intron_variant				ENSP00000499539.1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000194

AC:

AN:

138894

Hom.:

AF XY:

0.000175

AC XY:

AN XY:

74390

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.000133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000970

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000387

Gnomad OTH exome

AF:

0.000253

GnomAD4 exome

AF:

0.000437

AC:

239

AN:

547366

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

112

AN XY:

294782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000151

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00448

Gnomad4 SAS exome

AF:

0.0000825

Gnomad4 FIN exome

AF:

0.0000422

Gnomad4 NFE exome

AF:

0.000271

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000342

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000389

Hom.:

Bravo

AF:

0.000272

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cone dystrophy 3

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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