CRX p.Pro7Pro

Variant names:

• chr19-47834461-C-C
• NM_000554.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-47834462--
• chr19-47834464-G-T
• chr19-47834464-G-C
• chr19-47834464-G-A

Variant summary

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

The NM_000554.6(CRX):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CRX NM_000554.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78
• Publications: 0 publications found

Genes affected

CRX (HGNC:2383): (cone-rod homeobox) The protein encoded by this gene is a photoreceptor-specific transcription factor which plays a role in the differentiation of photoreceptor cells. This homeodomain protein is necessary for the maintenance of normal cone and rod function. Mutations in this gene are associated with photoreceptor degeneration, Leber congenital amaurosis type III and the autosomal dominant cone-rod dystrophy 2. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. [provided by RefSeq, Jul 2008]

CRX Gene-Disease associations (from GenCC):

• cone-rod dystrophy 2

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• hereditary macular dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Leber congenital amaurosis 7

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000554.6. 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
	CRX	NM_000554.6	MANE Select	c.		exon_region	Exon 4 of 4	NP_000545.1	O43186
	CRX	NM_000554.6	MANE Select	c.		3_prime_UTR	Exon 4 of 4	NP_000545.1	O43186

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRX	ENST00000221996.12	TSL:2 MANE Select	c.		splice_donor intron	N/A	ENSP00000221996.5	O43186
	CRX	ENST00000556527.1	TSL:1	n.		intron	N/A
	CRX	ENST00000566686.5	TSL:5	c.		splice_donor intron	N/A	ENSP00000457808.2	H3BUU7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-48337718;