Variant 1-211477053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164688.2(RD3):c.*1983C>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 0.000539 in 151,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RD3
NM_001164688.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.726

Variant links:

Genes affected

RD3 (HGNC:19689): (RD3 regulator of GUCY2D) This gene encodes a retinal protein that is associated with promyelocytic leukemia-gene product (PML) bodies in the nucleus. Mutations in this gene cause Leber congenital amaurosis type 12, a disease that results in retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

RD3 links:

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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RD3	NM_001164688.2 linkuse as main transcript	c.*1983C>T		3_prime_UTR_variant	3/3	ENST00000680073.1	NP_001158160.1
RD3	NM_183059.3 linkuse as main transcript	c.*1983C>T		3_prime_UTR_variant	3/3		NP_898882.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
RD3	ENST00000680073.1 linkuse as main transcript	c.*1983C>T	3_prime_UTR_variant	3/3		NM_001164688.2	ENSP00000505312	P1
RD3	ENST00000367002.5 linkuse as main transcript	c.*1983C>T	3_prime_UTR_variant	3/3	1		ENSP00000355969	P1
RD3	ENST00000484910.1 linkuse as main transcript	n.2539C>T	non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.000540

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.000285

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

GnomAD4 genome

AF:

0.000539

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000285

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.000397

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leber congenital amaurosis 12

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over