NM_000327.4:c.339delG

Variant names:

Variant summary

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

The NM_000327.4(ROM1):c.339delG(p.Leu114SerfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,579,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G113G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ROM1
NM_000327.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.35

Publications

14 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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 7
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ROM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 26 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROM1	NM_000327.4 link	c.339delG	p.Leu114SerfsTer8	frameshift_variant	Exon 1 of 3	ENST00000278833.4	NP_000318.2	Q03395

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ROM1	ENST00000278833.4 link	c.339delG	p.Leu114SerfsTer8	frameshift_variant	Exon 1 of 3	1	NM_000327.4	ENSP00000278833.3	Q03395
ROM1	ENST00000525947.1 link	c.-194delG		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000432983.1	E9PMR7
ROM1	ENST00000534093.5 link	c.-38-638delG		intron_variant	Intron 1 of 2	2		ENSP00000432151.1	E9PS24
ROM1	ENST00000525801.1 link	c.-38-638delG		intron_variant	Intron 1 of 1	3		ENSP00000433566.1	E9PKF5

Frequencies

GnomAD3 genomes

AF:

0.000172

AC:

AN:

150740

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000583

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000192

Gnomad OTH

AF:

0.000489

GnomAD2 exomes

AF:

0.000489

AC:

105

AN:

214556

AF XY:

0.000381

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000475

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.000733

Gnomad NFE exome

AF:

0.000462

Gnomad OTH exome

AF:

0.000373

GnomAD4 exome

AF:

0.000200

AC:

286

AN:

1428952

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

149

AN XY:

710788

show subpopulations

African (AFR)

AF:

0.000274

AC:

AN:

32798

American (AMR)

AF:

0.000413

AC:

AN:

43590

Ashkenazi Jewish (ASJ)

AF:

0.0000389

AC:

AN:

25682

East Asian (EAS)

AF:

0.000360

AC:

AN:

38892

South Asian (SAS)

AF:

0.0000588

AC:

AN:

85008

European-Finnish (FIN)

AF:

0.000281

AC:

AN:

49854

Middle Eastern (MID)

AF:

0.000356

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.000197

AC:

214

AN:

1088334

Other (OTH)

AF:

0.000152

AC:

AN:

59174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000172

AC:

AN:

150856

Hom.:

Cov.:

AF XY:

0.0000814

AC XY:

AN XY:

73674

show subpopulations

African (AFR)

AF:

0.000219

AC:

AN:

41104

American (AMR)

AF:

0.00

AC:

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.000585

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000192

AC:

AN:

67554

Other (OTH)

AF:

0.000484

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000737

Hom.:

Bravo

AF:

0.000234

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 7

Uncertain:1

Mar 11, 2020

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Jan 14, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change creates a premature translational stop signal (p.Leu114Serfs*8) in the ROM1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ROM1 cause disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with retinal dystrophy (PMID: 26103963, 31054281). ClinVar contains an entry for this variant (Variation ID: 960408). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Retinal dystrophy

Uncertain:1

Jan 01, 2022

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=29/171

disease causing (fs/PTC)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over