chr11-62612953-G-T

Variant names:

• chr11-62612953-G-T
• rs3923805
• ENST00000964791.1:c.-496C>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The ENST00000964791.1(EML3):​c.-496C>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 0.225 in 438,270 control chromosomes in the GnomAD database, including 12,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3766 hom., cov: 33)
  • Exomes 𝑓: 0.23 (8763 hom.)
• Consequence: EML3 ENST00000964791.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0590
• Publications: 11 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: Benign. The variant received -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 11-62612953-G-T is Benign according to our data. Variant chr11-62612953-G-T is described in ClinVar as Benign. ClinVar VariationId is 305156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

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.-496C>A		upstream_gene	N/A	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.-496C>A		upstream_gene	N/A	NP_001287722.1
	EML3	NM_001300794.2		c.-496C>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.-496C>A		5_prime_UTR	Exon 1 of 22	ENSP00000634850.1
	ROM1	ENST00000534093.5	TSL:2	c.-39+1033G>T		intron	N/A	ENSP00000432151.1	E9PS24
	ROM1	ENST00000525801.1	TSL:3	c.-39+862G>T		intron	N/A	ENSP00000433566.1	E9PKF5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31755 AN: 151768 Hom.: 3762 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.233 AC: 66659 AN: 286388 Hom.: 8763 Cov.: 0 AF XY: 0.229 AC XY: 34266 AN XY: 149576

African (AFR) AF: 0.127 AC: 1139 AN: 8978

American (AMR) AF: 0.140 AC: 1373 AN: 9776

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 2458 AN: 9342

East Asian (EAS) AF: 0.0493 AC: 936 AN: 18980

South Asian (SAS) AF: 0.170 AC: 5001 AN: 29404

European-Finnish (FIN) AF: 0.198 AC: 3612 AN: 18216

Middle Eastern (MID) AF: 0.260 AC: 339 AN: 1306

European-Non Finnish (NFE) AF: 0.276 AC: 47853 AN: 173240

Other (OTH) AF: 0.230 AC: 3948 AN: 17146

GnomAD4 genome AF: 0.209 AC: 31768 AN: 151882 Hom.: 3766 Cov.: 33 AF XY: 0.204 AC XY: 15163 AN XY: 74252

African (AFR) AF: 0.136 AC: 5624 AN: 41482

American (AMR) AF: 0.172 AC: 2632 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3464

East Asian (EAS) AF: 0.0518 AC: 265 AN: 5114

South Asian (SAS) AF: 0.159 AC: 769 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1935 AN: 10592

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18871 AN: 67816

Other (OTH) AF: 0.236 AC: 497 AN: 2108

Alfa AF: 0.240 Hom.: 615

Bravo AF: 0.205

Asia WGS AF: 0.109 AC: 384 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.059
PromoterAI		-0.084	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.58		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.58		Position offset: -2

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

Other links and lift over

dbSNP: rs3923805; hg19: chr11-62380425;