rs34116882

Variant names:

• chr14-21345126-C-G
• NM_020366.4:c.3546C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-21345126-C-G
• chr14-21345126-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_020366.4(RPGRIP1):​c.3546C>G​(p.Asp1182Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D1182D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPGRIP1 NM_020366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

Genes affected

RPGRIP1 (HGNC:13436): (RPGR interacting protein 1) This gene encodes a photoreceptor protein that interacts with retinitis pigmentosa GTPase regulator protein and is a key component of cone and rod photoreceptor cells. Mutations in this gene lead to autosomal recessive congenital blindness. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a region_of_interest Interaction with RPGR (size 190) in uniprot entity RPGR1_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_020366.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPGRIP1	NM_020366.4	c.3546C>G	p.Asp1182Glu	missense_variant	Exon 23 of 25	ENST00000400017.7	NP_065099.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPGRIP1	ENST00000400017.7	c.3546C>G	p.Asp1182Glu	missense_variant	Exon 23 of 25	1	NM_020366.4	ENSP00000382895.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;D;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	T;T;T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.2	.;.;M;.;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.4	D;D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.060	T;D;D;T;D
Polyphen		1.0, 1.0, 1.0	.;.;D;D;D
Vest4		0.73
MutPred		0.39		.;.;Gain of ubiquitination at K1177 (P = 0.1204);.;.;
MVP		0.87
MPC		0.32
ClinPred		0.98	D
GERP RS		2.2
Varity_R		0.56
gMVP		0.48

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: chr14-21813285;