6-158314251-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020245.5(TULP4):​c.235C>T​(p.Arg79Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TULP4
NM_020245.5 missense

Scores

8
4
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
Variant links:
Genes affected
TULP4 (HGNC:15530): (TUB like protein 4) Predicted to be involved in protein ubiquitination. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TULP4NM_020245.5 linkuse as main transcriptc.235C>T p.Arg79Trp missense_variant 1/14 ENST00000367097.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TULP4ENST00000367097.8 linkuse as main transcriptc.235C>T p.Arg79Trp missense_variant 1/141 NM_020245.5 P1Q9NRJ4-1
TULP4ENST00000367094.6 linkuse as main transcriptc.235C>T p.Arg79Trp missense_variant 1/131 Q9NRJ4-2
ENST00000619713.1 linkuse as main transcriptn.20+31391C>T intron_variant, non_coding_transcript_variant 5
TULP4ENST00000616856.1 linkuse as main transcriptn.807C>T non_coding_transcript_exon_variant 1/82

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249126
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134820
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461474
Hom.:
0
Cov.:
35
AF XY:
0.0000193
AC XY:
14
AN XY:
726956
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000330
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 17, 2024The c.235C>T (p.R79W) alteration is located in exon 1 (coding exon 1) of the TULP4 gene. This alteration results from a C to T substitution at nucleotide position 235, causing the arginine (R) at amino acid position 79 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;.
Eigen
Benign
0.15
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.079
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.54
T
MutationAssessor
Benign
1.9
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-7.8
D;D
REVEL
Uncertain
0.49
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.77
MVP
0.66
MPC
2.3
ClinPred
0.99
D
GERP RS
2.4
Varity_R
0.86
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1324493664; hg19: chr6-158735283; COSMIC: COSV100893494; COSMIC: COSV100893494; API