rs145601298

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178857.6(RP1L1):​c.*332G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 170,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RP1L1
NM_178857.6 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300
Variant links:
Genes affected
RP1L1 (HGNC:15946): (RP1 like 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, and two C-terminal large repetitive regions, both of which contain a high percentage of glutamine and glutamic acid residues. This protein is a retinal-specific protein. Its exact length varies among individuals due to the presence of a 16aa repeat in the first C-terminal repetitive region. The 16aa repeat is encoded by the highly polymorphic 48-bp repeat, and 1-6 copies of the 16aa repeat have been identified in normal individuals. The current reference sequence shown here has a single copy of the 16aa repeat. This protein and the RP1 protein, another retinal-specific protein, play essential and synergistic roles in affecting photosensitivity and outer segment morphogenesis of rod photoreceptors. Mutations in this gene cause occult macular dystrophy (OMD). [provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RP1L1NM_178857.6 linkc.*332G>T 3_prime_UTR_variant Exon 4 of 4 ENST00000382483.4 NP_849188.4 Q8IWN7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RP1L1ENST00000382483 linkc.*332G>T 3_prime_UTR_variant Exon 4 of 4 1 NM_178857.6 ENSP00000371923.3 Q8IWN7-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.0000117
AC:
2
AN:
170236
Hom.:
0
Cov.:
2
AF XY:
0.00
AC XY:
0
AN XY:
89488
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000116
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000941
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.6
DANN
Benign
0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-10464073; API