Variant 6-158479754-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020245.5(TULP4):c.1030C>T(p.Pro344Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,460,516 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TULP4
NM_020245.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

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]

TULP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP4	NM_020245.5 linkuse as main transcript	c.1030C>T	p.Pro344Ser	missense_variant	7/14	ENST00000367097.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP4	ENST00000367097.8 linkuse as main transcript	c.1030C>T	p.Pro344Ser	missense_variant	7/14	1	NM_020245.5	P1	Q9NRJ4-1
TULP4	ENST00000367094.6 linkuse as main transcript	c.1030C>T	p.Pro344Ser	missense_variant	7/13	1			Q9NRJ4-2
TULP4	ENST00000616856.1 linkuse as main transcript	n.1602C>T		non_coding_transcript_exon_variant	7/8	2
TULP4	ENST00000613390.1 linkuse as main transcript	c.85C>T	p.Pro29Ser	missense_variant, NMD_transcript_variant	2/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000721

AC:

AN:

249738

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460516

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000403

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000741

AC:

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 submitter

clinical testing

Ambry Genetics

May 12, 2024

The c.1030C>T (p.P344S) alteration is located in exon 7 (coding exon 7) of the TULP4 gene. This alteration results from a C to T substitution at nucleotide position 1030, causing the proline (P) at amino acid position 344 to be replaced by a serine (S). 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

Benign

0.24

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.71

P;P

Vest4

0.77

MutPred

0.52

Gain of catalytic residue at P344 (P = 0.0367);Gain of catalytic residue at P344 (P = 0.0367);

MVP

0.27

MPC

0.86

ClinPred

0.31

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.40

gMVP

0.67

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over