chr3-129528771-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_000539.3(RHO):​c.38T>C​(p.Phe13Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RHO
NM_000539.3 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25
Variant links:
Genes affected
RHO (HGNC:10012): (rhodopsin) The protein encoded by this gene is found in rod cells in the back of the eye and is essential for vision in low-light conditions. The encoded protein binds to 11-cis retinal and is activated when light hits the retinal molecule. Defects in this gene are a cause of congenital stationary night blindness. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 11 uncertain in NM_000539.3
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RHONM_000539.3 linkuse as main transcriptc.38T>C p.Phe13Ser missense_variant 1/5 ENST00000296271.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RHOENST00000296271.4 linkuse as main transcriptc.38T>C p.Phe13Ser missense_variant 1/51 NM_000539.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitterresearchDept Of Ophthalmology, Nagoya UniversityOct 01, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
D
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.24
D
MetaRNN
Uncertain
0.50
D
MetaSVM
Uncertain
0.51
D
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.97
N
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.19
T
Polyphen
0.54
P
Vest4
0.39
MutPred
0.58
Gain of disorder (P = 0.0054);
MVP
0.95
MPC
0.48
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.76
gMVP
0.93

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: chr3-129247614; API