rs147295026

chr16-53671541-A-Cchr16-53671541-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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=0.42107022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPGRIP1L	NM_015272.5	c.1072T>G	p.Leu358Val	missense_variant	9/27	ENST00000647211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPGRIP1L	ENST00000647211.2	c.1072T>G	p.Leu358Val	missense_variant	9/27		NM_015272.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249498 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134848

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 SAS exome AF: 0.0000329

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: 1 AN: 1427146 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 712026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	D
BayesDel_noAF	Pathogenic	0.18
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.83	T;.;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.42	T;T;T;T;T;T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Pathogenic	3.0	M;M;.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
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	D
GERP RS		5.8
Varity_R		0.68
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs147295026; hg19: chr16-53705453;