11-62612797-AG-AGG

Variant names:

• chr11-62612797-A-AG
• rs886048436
• ENST00000964791.1:c.-341dupC

Variant summary

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

The ENST00000964791.1(EML3):​c.-341dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000396 in 277,726 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: EML3 ENST00000964791.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 0 publications found

Genes affected

EML3 (HGNC:26666): (EMAP like 3) Predicted to enable microtubule binding activity. Involved in mitotic metaphase plate congression and regulation of mitotic spindle assembly. Located in several cellular components, including midbody; mitotic spindle microtubule; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ROM1 (HGNC:10254): (retinal outer segment membrane protein 1) This gene is a member of a photoreceptor-specific gene family and encodes an integral membrane protein found in the photoreceptor disk rim of the eye. This protein can form homodimers or can heterodimerize with another photoreceptor, retinal degeneration slow (RDS). It is essential for disk morphogenesis, and may also function as an adhesion molecule involved in the stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. Certain defects in this gene have been associated with the degenerative eye disease retinitis pigmentosa. [provided by RefSeq, Jul 2008]

ROM1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 7

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 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: ENST00000964791.1. 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
	EML3	NM_153265.3	MANE Select	c.-341_-340insC		upstream_gene	N/A	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.-341_-340insC		upstream_gene	N/A	NP_001287722.1
	EML3	NM_001300794.2		c.-341_-340insC		upstream_gene	N/A	NP_001287723.1	Q32P44-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML3	ENST00000964791.1		c.-341dupC		5_prime_UTR	Exon 1 of 22	ENSP00000634850.1
	EML3	ENST00000859376.1		c.-341dupC		5_prime_UTR	Exon 1 of 21	ENSP00000529435.1
	ROM1	ENST00000534093.5	TSL:2	c.-39+884dupG		intron	N/A	ENSP00000432151.1	E9PS24

Frequencies

GnomAD3 genomes AF: 0.0000470 AC: 7 AN: 149034 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000497

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: 0.0000747

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000311 AC: 4 AN: 128692 Hom.: 0 Cov.: 0 AF XY: 0.0000460 AC XY: 3 AN XY: 65200

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3590

American (AMR) AF: 0.00 AC: 0 AN: 3604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4808

East Asian (EAS) AF: 0.00 AC: 0 AN: 10312

South Asian (SAS) AF: 0.00 AC: 0 AN: 2376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 700

European-Non Finnish (NFE) AF: 0.0000477 AC: 4 AN: 83784

Other (OTH) AF: 0.00 AC: 0 AN: 8622

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0310196), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000470 AC: 7 AN: 149034 Hom.: 0 Cov.: 33 AF XY: 0.0000412 AC XY: 3 AN XY: 72864

African (AFR) AF: 0.0000497 AC: 2 AN: 40260

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3436

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000747 AC: 5 AN: 66900

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63

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: rs886048436; hg19: chr11-62380269;