6-42162912-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384994.1(CIMIP3):​c.10-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 614,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: CIMIP3 NM_001384994.1 splice_region, intron
• Scores: Splicing: ADA: 0.00007632
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>G		splice_region intron	N/A	NP_001371923.1	X6R8D5-1
	GUCA1ANB-GUCA1A	NM_000409.5		c.-457-8C>G		splice_region intron	N/A	NP_000400.2
	GUCA1ANB-GUCA1A	NM_001319061.2		c.-828-8C>G		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>G		splice_region intron	N/A	ENSP00000485219.1	X6R8D5-1
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-282+7319C>G		intron	N/A	ENSP00000499539.1
	CIMIP3	ENST00000372963.4	TSL:2	c.55-8C>G		splice_region intron	N/A	ENSP00000362054.3	X6R8D5-2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 80556 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000259 AC: 12 AN: 462680 Hom.: 0 Cov.: 0 AF XY: 0.0000205 AC XY: 5 AN XY: 243662

African (AFR) AF: 0.00 AC: 0 AN: 12310

American (AMR) AF: 0.00 AC: 0 AN: 21640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14186

East Asian (EAS) AF: 0.00 AC: 0 AN: 29668

South Asian (SAS) AF: 0.0000424 AC: 2 AN: 47224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3634

European-Non Finnish (NFE) AF: 0.0000380 AC: 10 AN: 263154

Other (OTH) AF: 0.00 AC: 0 AN: 26034

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152096 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74282

African (AFR) AF: 0.0000725 AC: 3 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.45
PhyloP100		0.030

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000076
dbscSNV1_RF	Benign	0.012
SpliceAI score (max)		0.15		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;