16-53692201-T-C

Position:

• chr16-53692201-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015272.5(RPGRIP1L):​c.394A>G​(p.Arg132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: RPGRIP1L NM_015272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34837192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.394A>G	p.Arg132Gly	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	c.394A>G	p.Arg132Gly	missense_variant	4/27		NM_015272.5	ENSP00000493946

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;T;.;.;.;.
Eigen	Benign	-0.045
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;.;D;D;D;D;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.35	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.5	M;M;.;M;.;.;.
MutationTaster	Benign	0.77	D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.2	D;.;.;D;D;D;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0030	D;.;.;D;D;D;D
Sift4G	Uncertain	0.0050	D;.;D;D;D;D;D
Polyphen		0.90	P;B;.;B;.;.;.
Vest4		0.48
MutPred		0.21		Gain of ubiquitination at K137 (P = 0.0276);Gain of ubiquitination at K137 (P = 0.0276);Gain of ubiquitination at K137 (P = 0.0276);Gain of ubiquitination at K137 (P = 0.0276);Gain of ubiquitination at K137 (P = 0.0276);Gain of ubiquitination at K137 (P = 0.0276);Gain of ubiquitination at K137 (P = 0.0276);
MVP		0.70
MPC		0.15
ClinPred		0.98	D
GERP RS		2.0
Varity_R		0.49
gMVP		0.53

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: chr16-53726113;