rs71458427

chr11-62613611-TGGGGGGG-Tchr11-62613611-TGGGGGGG-TGGGGGGchr11-62613611-TGGGGGGG-TGGGGGGGGchr11-62613611-TGGGGGGG-TGGGGGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000327.4(ROM1):c.333_339del(p.Gly112SerfsTer8) variant causes a frameshift change. The variant allele was found at a frequency of 0.000168 in 1,580,936 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G111G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: ROM1 NM_000327.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROM1	NM_000327.4	c.333_339del	p.Gly112SerfsTer8	frameshift_variant	1/3	ENST00000278833.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROM1	ENST00000278833.4	c.333_339del	p.Gly112SerfsTer8	frameshift_variant	1/3	1	NM_000327.4	P1
ROM1	ENST00000525947.1	c.-200_-194del		5_prime_UTR_variant	1/3	3
ROM1	ENST00000525801.1	c.-38-644_-38-638del		intron_variant		3
ROM1	ENST00000534093.5	c.-38-644_-38-638del		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 20 AN: 150742 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00423

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000326 AC: 70 AN: 214556 Hom.: 0 AF XY: 0.000465 AC XY: 55 AN XY: 118190

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 SAS exome AF: 0.00241

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.000172 AC: 246 AN: 1430078 Hom.: 1 AF XY: 0.000250 AC XY: 178 AN XY: 711384

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000229

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00275

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000152

GnomAD4 genome AF: 0.000133 AC: 20 AN: 150858 Hom.: 0 Cov.: 34 AF XY: 0.000217 AC XY: 16 AN XY: 73676

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00424

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71458427; hg19: chr11-62381083;