NM_015272.5:c.1843A>T

Variant names:

• chr16-53652844-T-A
• NM_015272.5:c.1843A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_015272.5(RPGRIP1L):​c.1843A>T​(p.Thr615Ser) 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. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T615P) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPGRIP1L NM_015272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-53652844-T-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1L	NM_015272.5	c.1843A>T	p.Thr615Ser	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.1843A>T	p.Thr615Ser	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	0.087
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.011	.;.;T;.;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	T;.;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.095	T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	0.52	N;N;.;N;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.91	N;.;.;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.24	T;.;.;T;T;T
Sift4G	Benign	0.46	T;.;T;T;T;T
Polyphen		0.0010	B;B;.;B;.;.
Vest4		0.22
MutPred		0.31		Gain of catalytic residue at T615 (P = 0.0176);Gain of catalytic residue at T615 (P = 0.0176);Gain of catalytic residue at T615 (P = 0.0176);Gain of catalytic residue at T615 (P = 0.0176);Gain of catalytic residue at T615 (P = 0.0176);Gain of catalytic residue at T615 (P = 0.0176);
MVP		0.60
MPC		0.066
ClinPred		0.076	T
GERP RS		3.1
Varity_R		0.049
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: 4

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: chr16-53686756; COSMIC: COSV100046511; COSMIC: COSV100046511;