Genetic Variant ENST00000534093.5:c.-39+1061C>T (chr11-62612981-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000534093.5(ROM1):c.-39+1061C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 366,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ROM1
ENST00000534093.5 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.612

Publications

0 publications found

Variant links:

Genes affected

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 links:

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]

EML3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000534093.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EML3	NM_153265.3	MANE Select	c.-524G>A	upstream_gene	N/A	NP_694997.2	Q32P44-1
EML3	NM_001300793.2		c.-524G>A	upstream_gene	N/A	NP_001287722.1
EML3	NM_001300794.2		c.-524G>A	upstream_gene	N/A	NP_001287723.1	Q32P44-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ROM1	ENST00000534093.5	TSL:2	c.-39+1061C>T	intron	N/A	ENSP00000432151.1	E9PS24
ROM1	ENST00000525801.1	TSL:3	c.-39+890C>T	intron	N/A	ENSP00000433566.1	E9PKF5
EML3	ENST00000394773.7	TSL:1 MANE Select	c.-524G>A	upstream_gene	N/A	ENSP00000378254.2	Q32P44-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000273

AC:

AN:

366760

Hom.:

Cov.:

AF XY:

0.00000523

AC XY:

AN XY:

191138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10984

American (AMR)

AF:

0.00

AC:

AN:

12946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11806

East Asian (EAS)

AF:

0.00

AC:

AN:

25420

South Asian (SAS)

AF:

0.00

AC:

AN:

34772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1664

European-Non Finnish (NFE)

AF:

0.00000449

AC:

AN:

222524

Other (OTH)

AF:

0.00

AC:

AN:

21982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.8

(source)

DANN

Benign

0.93

PhyloP100

-0.61

PromoterAI

0.027

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over