Variant 16-53638443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015272.5(RPGRIP1L):c.2959-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,132,226 control chromosomes in the GnomAD database, including 66,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.39 ( 13699 hom., cov: 32)

Exomes 𝑓: 0.31 ( 53031 hom. )

Consequence

RPGRIP1L
NM_015272.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0300

Variant links:

Genes affected

RPGRIP1L (HGNC:29168): (RPGRIP1 like) The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). [provided by RefSeq, Jun 2016]

RPGRIP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-53638443-C-T is Benign according to our data. Variant chr16-53638443-C-T is described in ClinVar as [Benign]. Clinvar id is 126276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 linkuse as main transcript	c.2959-32G>A		intron_variant		ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2 linkuse as main transcript	c.2959-32G>A		intron_variant			NM_015272.5	ENSP00000493946		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59571

AN:

151608

Hom.:

13650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.587

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.293

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.339

AC:

82446

AN:

243214

Hom.:

16138

AF XY:

0.340

AC XY:

44760

AN XY:

131710

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.226

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.603

Gnomad SAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.183

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.311

AC:

305082

AN:

980502

Hom.:

53031

Cov.:

AF XY:

0.316

AC XY:

160478

AN XY:

508266

show subpopulations

Gnomad4 AFR exome

AF:

0.636

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.401

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.283

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.393

AC:

59678

AN:

151724

Hom.:

13699

Cov.:

AF XY:

0.388

AC XY:

28798

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.626

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.587

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.293

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.346

Hom.:

3274

Bravo

AF:

0.409

Asia WGS

AF:

0.500

AC:

1737

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 12, 2024

- -

Joubert syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Meckel syndrome, type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.7

DANN

Benign

0.39

BranchPoint Hunter

0.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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