NM_000327.4:c.81G>T

Variant names:

• chr11-62613362-G-T
• rs148196509
• NM_000327.4:c.81G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_000327.4(ROM1):​c.81G>T​(p.Leu27Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,472 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0021 (11 hom.)
• Consequence: ROM1 NM_000327.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:5
• Conservation: PhyloP100: -0.169
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-62613362-G-T is Benign according to our data. Variant chr11-62613362-G-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 193086.
• BP7: Synonymous conserved (PhyloP=-0.169 with no splicing effect.
• BS2: High AC in GnomAd4 at 220 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.81G>T	p.Leu27Leu	synonymous	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.81G>T	p.Leu27Leu	synonymous	Exon 1 of 3	ENSP00000278833.3	Q03395
	ROM1	ENST00000534093.5	TSL:2	c.-38-896G>T		intron	N/A	ENSP00000432151.1	E9PS24
	ROM1	ENST00000525801.1	TSL:3	c.-38-896G>T		intron	N/A	ENSP00000433566.1	E9PKF5

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 220 AN: 152232 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00270

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00126 AC: 312 AN: 247872 AF XY: 0.00123

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.000436

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000435

Gnomad NFE exome AF: 0.00229

Gnomad OTH exome AF: 0.000998

GnomAD4 exome AF: 0.00209 AC: 3047 AN: 1461122 Hom.: 11 Cov.: 77 AF XY: 0.00207 AC XY: 1502 AN XY: 726866

African (AFR) AF: 0.000239 AC: 8 AN: 33468

American (AMR) AF: 0.000448 AC: 20 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000696 AC: 60 AN: 86146

European-Finnish (FIN) AF: 0.000620 AC: 33 AN: 53216

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5742

European-Non Finnish (NFE) AF: 0.00254 AC: 2829 AN: 1111776

Other (OTH) AF: 0.00157 AC: 95 AN: 60320

GnomAD4 genome AF: 0.00144 AC: 220 AN: 152350 Hom.: 1 Cov.: 34 AF XY: 0.00123 AC XY: 92 AN XY: 74494

African (AFR) AF: 0.000337 AC: 14 AN: 41592

American (AMR) AF: 0.00124 AC: 19 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00270 AC: 184 AN: 68026

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

Alfa AF: 0.00193 Hom.: 0

Bravo AF: 0.00127

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00202

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	-	1	not specified (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		-0.17
PromoterAI		-0.0042	Neutral
Mutation Taster		=100/0	polymorphism

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: rs148196509; hg19: chr11-62380834;