11-62612788-G-A

Variant names:

• chr11-62612788-G-A
• rs3825019
• ENST00000964791.1:c.-331C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS1

The ENST00000964791.1(EML3):​c.-331C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 151,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (11 hom.)
  • Failed GnomAD Quality Control
• Consequence: EML3 ENST00000964791.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.785
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 11-62612788-G-A is Benign according to our data. Variant chr11-62612788-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 305152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00122 (186/151888) while in subpopulation EAS AF = 0.0237 (122/5144). AF 95% confidence interval is 0.0203. There are 1 homozygotes in GnomAd4. There are 110 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.-331C>T		upstream_gene	N/A	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.-331C>T		upstream_gene	N/A	NP_001287722.1
	EML3	NM_001300794.2		c.-331C>T		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.-331C>T		5_prime_UTR	Exon 1 of 22	ENSP00000634850.1
	EML3	ENST00000859377.1		c.-331C>T		5_prime_UTR	Exon 1 of 22	ENSP00000529436.1
	EML3	ENST00000859376.1		c.-331C>T		5_prime_UTR	Exon 1 of 21	ENSP00000529435.1

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 186 AN: 151780 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000664

Gnomad OTH AF: 0.000956

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00162 AC: 247 AN: 152434 Hom.: 11 Cov.: 0 AF XY: 0.00159 AC XY: 123 AN XY: 77454

African (AFR) AF: 0.00 AC: 0 AN: 4176

American (AMR) AF: 0.000230 AC: 1 AN: 4352

Ashkenazi Jewish (ASJ) AF: 0.00234 AC: 13 AN: 5554

East Asian (EAS) AF: 0.0129 AC: 156 AN: 12076

South Asian (SAS) AF: 0.00102 AC: 3 AN: 2946

European-Finnish (FIN) AF: 0.000384 AC: 5 AN: 13032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 822

European-Non Finnish (NFE) AF: 0.000603 AC: 60 AN: 99464

Other (OTH) AF: 0.000899 AC: 9 AN: 10012

GnomAD4 genome AF: 0.00122 AC: 186 AN: 151888 Hom.: 1 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74256

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.000327 AC: 5 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.0237 AC: 122 AN: 5144

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10566

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

European-Non Finnish (NFE) AF: 0.000664 AC: 45 AN: 67804

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.00179

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.97
PhyloP100		0.79
PromoterAI		-0.043	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3825019; hg19: chr11-62380260;