16-53652637-G-C

Variant names:

• chr16-53652637-G-C
• NM_015272.5:c.2050C>G

Variant summary

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

The NM_015272.5(RPGRIP1L):​c.2050C>G​(p.Gln684Glu) 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: 33)
• Consequence: RPGRIP1L NM_015272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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=0.3597684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.2050C>G	p.Gln684Glu	missense_variant	Exon 15 of 27	ENST00000647211.2	NP_056087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.2050C>G	p.Gln684Glu	missense_variant	Exon 15 of 27		NM_015272.5	ENSP00000493946.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;.;T;.;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;.;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.36	T;T;T;T;T;T
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	2.0	M;M;.;M;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N;.;.;N;N;N
REVEL	Uncertain	0.59
Sift	Benign	0.50	T;.;.;T;T;T
Sift4G	Uncertain	0.047	D;.;T;D;D;D
Polyphen		0.81	P;P;.;P;.;.
Vest4		0.37
MutPred		0.43		Gain of disorder (P = 0.0559);Gain of disorder (P = 0.0559);Gain of disorder (P = 0.0559);Gain of disorder (P = 0.0559);Gain of disorder (P = 0.0559);Gain of disorder (P = 0.0559);
MVP		0.69
MPC		0.094
ClinPred		0.79	D
GERP RS		4.8
Varity_R		0.20
gMVP		0.78

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: chr16-53686549;