11-62612783-G-T

Variant names:

• chr11-62612783-G-T
• rs539586649
• ENST00000964791.1:c.-326C>A

Variant summary

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

The ENST00000964791.1(EML3):​c.-326C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 312,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: EML3 ENST00000964791.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).

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.-326C>A		upstream_gene	N/A	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.-326C>A		upstream_gene	N/A	NP_001287722.1
	EML3	NM_001300794.2		c.-326C>A		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.-326C>A		5_prime_UTR	Exon 1 of 22	ENSP00000634850.1
	EML3	ENST00000859377.1		c.-326C>A		5_prime_UTR	Exon 1 of 22	ENSP00000529436.1
	EML3	ENST00000859376.1		c.-326C>A		5_prime_UTR	Exon 1 of 21	ENSP00000529435.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151952 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000125 AC: 2 AN: 160604 Hom.: 0 Cov.: 0 AF XY: 0.0000245 AC XY: 2 AN XY: 81560

African (AFR) AF: 0.00 AC: 0 AN: 4350

American (AMR) AF: 0.00 AC: 0 AN: 4546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5818

East Asian (EAS) AF: 0.00 AC: 0 AN: 12984

South Asian (SAS) AF: 0.00 AC: 0 AN: 3166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 876

European-Non Finnish (NFE) AF: 0.00000958 AC: 1 AN: 104436

Other (OTH) AF: 0.0000947 AC: 1 AN: 10560

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152060 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74346

African (AFR) AF: 0.0000482 AC: 2 AN: 41508

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67882

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.95
PhyloP100		1.7
PromoterAI		-0.069	Neutral

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: rs539586649; hg19: chr11-62380255;