rs1387102485

Variant names:

• chr11-62613517-T-TG
• rs1387102485
• NM_000327.4:c.239dupG

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000327.4(ROM1):​c.239dupG​(p.Val81CysfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,532 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ROM1 NM_000327.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: -0.179
• Publications: 3 publications found

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 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 16 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000327.4. 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
	ROM1	NM_000327.4	MANE Select	c.239dupG	p.Val81CysfsTer51	frameshift	Exon 1 of 3	NP_000318.2	Q03395

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROM1	ENST00000278833.4	TSL:1 MANE Select	c.239dupG	p.Val81CysfsTer51	frameshift	Exon 1 of 3	ENSP00000278833.3	Q03395
	ROM1	ENST00000534093.5	TSL:2	c.-38-738dupG		intron	N/A	ENSP00000432151.1	E9PS24
	ROM1	ENST00000525801.1	TSL:3	c.-38-738dupG		intron	N/A	ENSP00000433566.1	E9PKF5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249204 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461532 Hom.: 0 Cov.: 77 AF XY: 0.0000124 AC XY: 9 AN XY: 727074

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111844

Other (OTH) AF: 0.0000166 AC: 1 AN: 60354

GnomAD4 genome Cov.: 34

Alfa AF: 0.000111 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
1	-	-	Retinitis pigmentosa 7, digenic (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
Mutation Taster		=34/166	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1387102485; hg19: chr11-62380989;