GeneBe

rs770045008

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong

The NM_003322.6(TULP1):ā€‹c.1256G>Cā€‹(p.Arg419Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R419Q) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

TULP1
NM_003322.6 missense

Scores

16
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.52
Variant links:
Genes affected
TULP1 (HGNC:12423): (TUB like protein 1) This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15. [provided by RefSeq, Nov 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr6-35503626-C-T is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.99

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TULP1NM_003322.6 linkc.1256G>C p.Arg419Pro missense_variant Exon 13 of 15 ENST00000229771.11 NP_003313.3 O00294-1Q0QD38
TULP1NM_001289395.2 linkc.1097G>C p.Arg366Pro missense_variant Exon 12 of 14 NP_001276324.1 O00294-2F1T0I9
LOC124901309XR_007059561.1 linkn.76-4601C>G intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TULP1ENST00000229771.11 linkc.1256G>C p.Arg419Pro missense_variant Exon 13 of 15 1 NM_003322.6 ENSP00000229771.6 O00294-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1446984
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
718228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.95
.;D;D
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Pathogenic
0.79
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.0
.;H;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-7.0
D;D;.
REVEL
Pathogenic
0.97
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.96
MutPred
0.91
.;Loss of MoRF binding (P = 0.0035);.;
MVP
0.96
MPC
0.69
ClinPred
1.0
D
GERP RS
4.3
Varity_R
0.99
gMVP
0.95

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: chr6-35471403; API