chr6-42162989-C-T

Variant names:

• chr6-42162989-C-T
• rs886061391
• NM_001384994.1:c.79C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384994.1(CIMIP3):​c.79C>T​(p.His27Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 562,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H27N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CIMIP3 NM_001384994.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080608934).

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.79C>T	p.His27Tyr	missense	Exon 2 of 2	NP_001371923.1	X6R8D5-1
	CIMIP3	NM_001370581.1		c.124C>T	p.His42Tyr	missense	Exon 2 of 2	NP_001357510.1	X6R8D5-2
	GUCA1ANB-GUCA1A	NM_000409.5		c.-388C>T		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.79C>T	p.His27Tyr	missense	Exon 2 of 2	ENSP00000485219.1	X6R8D5-1
	GUCA1ANB-GUCA1A	ENST00000654459.1		c.-282+7396C>T		intron	N/A	ENSP00000499539.1
	CIMIP3	ENST00000372963.4	TSL:2	c.124C>T	p.His42Tyr	missense	Exon 2 of 2	ENSP00000362054.3	X6R8D5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000178 AC: 1 AN: 562310 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 303302

African (AFR) AF: 0.00 AC: 0 AN: 15732

American (AMR) AF: 0.00 AC: 0 AN: 34506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19836

East Asian (EAS) AF: 0.00 AC: 0 AN: 32014

South Asian (SAS) AF: 0.00 AC: 0 AN: 62320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 315406

Other (OTH) AF: 0.0000327 AC: 1 AN: 30580

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.076
DANN	Benign	0.75
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.96	T
PhyloP100		-2.9
REVEL	Benign	0.016
Sift4G	Benign	0.63	T
Vest4		0.20
MVP		0.040
ClinPred		0.045	T
GERP RS		-0.51
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs886061391; hg19: chr6-42130727;