rs58894089

Variant names:

• chr6-42162912-C-T
• rs58894089
• NM_001384994.1:c.10-8C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-42162912-C-T
• chr6-42162912-C-A
• chr6-42162912-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384994.1(CIMIP3):​c.10-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 614,810 control chromosomes in the GnomAD database, including 1,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (782 hom., cov: 32)
  • Exomes 𝑓: 0.025 (352 hom.)
• Consequence: CIMIP3 NM_001384994.1 splice_region, intron
• Scores: Splicing: ADA: 0.00003861
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300
• Publications: 2 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-42162912-C-T is Benign according to our data. Variant chr6-42162912-C-T is described in ClinVar as Benign. ClinVar VariationId is 356686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

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.10-8C>T		splice_region intron	N/A	NP_001371923.1	X6R8D5-1
	GUCA1ANB-GUCA1A	NM_000409.5		c.-457-8C>T		splice_region intron	N/A	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.-828-8C>T		splice_region intron	N/A	NP_001305990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP3	ENST00000623004.2	TSL:3 MANE Select	c.10-8C>T		splice_region intron	N/A	ENSP00000485219.1	X6R8D5-1
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-282+7319C>T		intron	N/A	ENSP00000499539.1
	CIMIP3	ENST00000372963.4	TSL:2	c.55-8C>T		splice_region intron	N/A	ENSP00000362054.3	X6R8D5-2

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10202 AN: 152066 Hom.: 781 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0612

GnomAD2 exomes AF: 0.0285 AC: 2293 AN: 80556 AF XY: 0.0265

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.0214

Gnomad ASJ exome AF: 0.0244

Gnomad EAS exome AF: 0.000414

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.0237

GnomAD4 exome AF: 0.0252 AC: 11659 AN: 462626 Hom.: 352 Cov.: 0 AF XY: 0.0243 AC XY: 5918 AN XY: 243628

African (AFR) AF: 0.176 AC: 2170 AN: 12296

American (AMR) AF: 0.0247 AC: 535 AN: 21636

Ashkenazi Jewish (ASJ) AF: 0.0272 AC: 386 AN: 14186

East Asian (EAS) AF: 0.000135 AC: 4 AN: 29668

South Asian (SAS) AF: 0.0139 AC: 655 AN: 47214

European-Finnish (FIN) AF: 0.0134 AC: 602 AN: 44830

Middle Eastern (MID) AF: 0.0380 AC: 138 AN: 3634

European-Non Finnish (NFE) AF: 0.0238 AC: 6261 AN: 263130

Other (OTH) AF: 0.0349 AC: 908 AN: 26032

GnomAD4 genome AF: 0.0671 AC: 10218 AN: 152184 Hom.: 782 Cov.: 32 AF XY: 0.0639 AC XY: 4754 AN XY: 74398

African (AFR) AF: 0.182 AC: 7564 AN: 41472

American (AMR) AF: 0.0339 AC: 519 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4822

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0253 AC: 1719 AN: 68008

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0382 Hom.: 494

Bravo AF: 0.0744

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

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	-0.84
CADD	Benign	0.96
DANN	Benign	0.36
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs58894089; hg19: chr6-42130650;