rs121918200

Variant names:

• chr16-53652604-C-A
• NM_015272.5:c.2083G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-53652604-C-A
• chr16-53652604-C-G
• chr16-53652604-C-T

Variant summary

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

The NM_015272.5(RPGRIP1L):​c.2083G>T​(p.Ala695Ser) 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. 12/21 in silico tools predict 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: 0.863

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=0.27658048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.2083G>T	p.Ala695Ser	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.2083G>T	p.Ala695Ser	missense_variant	Exon 15 of 27		NM_015272.5	ENSP00000493946.1

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	0.11
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	.;.;T;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.79	T;.;T;T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Benign	1.3	L;L;.;L;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.6	N;.;.;N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.19	T;.;.;T;T;D
Sift4G	Benign	0.23	T;.;D;D;D;T
Polyphen		0.31	B;B;.;B;.;.
Vest4		0.56
MutPred		0.45		Gain of disorder (P = 0.067);Gain of disorder (P = 0.067);Gain of disorder (P = 0.067);Gain of disorder (P = 0.067);Gain of disorder (P = 0.067);Gain of disorder (P = 0.067);
MVP		0.73
MPC		0.099
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.078
gMVP		0.55

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: chr16-53686516;