Genetic Variant NM_015272.5:c.1072T>G (chr16-53671541-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015272.5(RPGRIP1L):c.1072T>G(p.Leu358Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,427,146 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. Synonymous variant affecting the same amino acid position (i.e. L358L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

RPGRIP1L
NM_015272.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Meckel syndrome, type 5
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Joubert syndrome 7
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
COACH syndrome 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with renal defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RPGRIP1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42107022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5 link	c.1072T>G	p.Leu358Val	missense_variant	Exon 9 of 27	ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2 link	c.1072T>G	p.Leu358Val	missense_variant	Exon 9 of 27		NM_015272.5	ENSP00000493946.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249498

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1427146

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32762

American (AMR)

AF:

0.00

AC:

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.00

AC:

AN:

39320

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082106

Other (OTH)

AF:

0.00

AC:

AN:

59162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Pathogenic

0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;.;T;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;.;T;T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.42

T;T;T;T;T;T

MetaSVM

Uncertain

0.71

MutationAssessor

Pathogenic

3.0

M;M;.;M;.;.

PhyloP100

1.2

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.4

N;.;.;D;N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.0070

D;.;.;D;D;D

Sift4G

Uncertain

0.036

D;.;D;D;D;D

Polyphen

1.0

D;D;.;D;.;.

Vest4

0.62

MutPred

0.14

Gain of methylation at K359 (P = 0.0329);Gain of methylation at K359 (P = 0.0329);Gain of methylation at K359 (P = 0.0329);Gain of methylation at K359 (P = 0.0329);Gain of methylation at K359 (P = 0.0329);Gain of methylation at K359 (P = 0.0329);

MVP

0.84

MPC

0.43

ClinPred

0.86

GERP RS

5.8

Varity_R

0.68

gMVP

0.46

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over