chr16-53692113-C-T

Position:

chr16-53692113-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The NM_015272.5(RPGRIP1L):c.482G>A(p.Arg161His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,613,968 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RPGRIP1L
NM_015272.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 2.38

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 -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010920078).

BP6

Variant 16-53692113-C-T is Benign according to our data. Variant chr16-53692113-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197303.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00108 (164/152118) while in subpopulation AFR AF= 0.00371 (154/41488). AF 95% confidence interval is 0.00323. There are 1 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 linkuse as main transcript	c.482G>A	p.Arg161His	missense_variant	4/27	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.482G>A	p.Arg161His	missense_variant	4/27		NM_015272.5	ENSP00000493946		Q68CZ1-1

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000306

AC:

AN:

251402

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00418

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

202

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00346

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

152118

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.0000746

Hom.:

Bravo

AF:

0.00130

ESP6500AA

AF:

0.00341

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000338

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 13, 2015	- -

Familial aplasia of the vermis

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 11, 2019

- -

RPGRIP1L-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 01, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.011

.;.;T;.;.;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;.;D;D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.011

T;T;T;T;T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.1

M;M;.;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.29

N;.;.;N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.041

D;.;.;T;T;T;D

Sift4G

Benign

0.19

T;.;T;D;D;T;T

Polyphen

1.0

D;B;.;B;.;.;.

Vest4

0.36

MVP

0.76

MPC

0.099

ClinPred

0.018

GERP RS

4.7

Varity_R

0.074

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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