rs34116882

Variant names:

• chr14-21345126-C-G
• rs34116882
• 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. The variant received 2 ACMG points: 2P and 0B. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1182V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPGRIP1 NM_020366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 0 publications found

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]

RPGRIP1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 13

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Leber congenital amaurosis 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• 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;.;.
PhyloP100		0.036
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
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs34116882; hg19: chr14-21813285;