rs886048436

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-62612797-AG-A
• chr11-62612797-AG-AGG

Variant summary

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

The ENST00000964791.1(EML3):​c.-341delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 277,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: EML3 ENST00000964791.1 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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.-341delC		upstream_gene	N/A	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.-341delC		upstream_gene	N/A	NP_001287722.1
	EML3	NM_001300794.2		c.-341delC		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.-341delC		5_prime_UTR	Exon 1 of 22	ENSP00000634850.1
	EML3	ENST00000859376.1		c.-341delC		5_prime_UTR	Exon 1 of 21	ENSP00000529435.1
	ROM1	ENST00000534093.5	TSL:2	c.-39+884delG		intron	N/A	ENSP00000432151.1	E9PS24

Frequencies

GnomAD3 genomes AF: 0.000228 AC: 34 AN: 149034 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

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: 0.000389

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000699 AC: 9 AN: 128682 Hom.: 0 Cov.: 0 AF XY: 0.0000614 AC XY: 4 AN XY: 65196

⚠️ 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: 3588

American (AMR) AF: 0.00 AC: 0 AN: 3602

Ashkenazi Jewish (ASJ) AF: 0.000208 AC: 1 AN: 4808

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 2374

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: 0.0000836 AC: 7 AN: 83780

Other (OTH) AF: 0.000116 AC: 1 AN: 8622

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000146298), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000228 AC: 34 AN: 149134 Hom.: 0 Cov.: 33 AF XY: 0.000219 AC XY: 16 AN XY: 72976

African (AFR) AF: 0.000149 AC: 6 AN: 40372

American (AMR) AF: 0.000132 AC: 2 AN: 15154

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5012

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000389 AC: 26 AN: 66890

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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;