NM_001384994.1:c.54G>A

Variant names:

• chr6-42162964-G-A
• rs144002571
• NM_001384994.1:c.54G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.418
• Publications: 1 publications found

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]

GUCA1ANB-GUCA1A (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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-0.418 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384994.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP3	NM_001384994.1	MANE Select	c.54G>A	p.Pro18Pro	synonymous	Exon 2 of 2	NP_001371923.1	X6R8D5-1
	CIMIP3	NM_001370581.1		c.99G>A	p.Pro33Pro	synonymous	Exon 2 of 2	NP_001357510.1	X6R8D5-2
	GUCA1ANB-GUCA1A	NM_000409.5		c.-413G>A		5_prime_UTR	Exon 2 of 6	NP_000400.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP3	ENST00000623004.2	TSL:3 MANE Select	c.54G>A	p.Pro18Pro	synonymous	Exon 2 of 2	ENSP00000485219.1	X6R8D5-1
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-282+7371G>A		intron	N/A	ENSP00000499539.1
	CIMIP3	ENST00000372963.4	TSL:2	c.99G>A	p.Pro33Pro	synonymous	Exon 2 of 2	ENSP00000362054.3	X6R8D5-2

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152130 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000194 AC: 27 AN: 138894 AF XY: 0.000175

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 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.: 0 Cov.: 0 AF XY: 0.000380 AC XY: 112 AN XY: 294782

African (AFR) AF: 0.00 AC: 0 AN: 15268

American (AMR) AF: 0.000151 AC: 5 AN: 33132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18918

East Asian (EAS) AF: 0.00448 AC: 141 AN: 31466

South Asian (SAS) AF: 0.0000825 AC: 5 AN: 60598

European-Finnish (FIN) AF: 0.0000422 AC: 2 AN: 47430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3988

European-Non Finnish (NFE) AF: 0.000271 AC: 83 AN: 306708

Other (OTH) AF: 0.000100 AC: 3 AN: 29858

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000417 AC XY: 31 AN XY: 74428

African (AFR) AF: 0.000265 AC: 11 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 67996

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000389 Hom.: 0

Bravo AF: 0.000272

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cone dystrophy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.64
PhyloP100		-0.42
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs144002571; hg19: chr6-42130702; COSMIC: COSV50003411;