Variant 3-9810266-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025930.5(TTLL3):c.260C>G(p.Pro87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,355,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

TTLL3
NM_001025930.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.644

Variant links:

Genes affected

TTLL3 (HGNC:24483): (tubulin tyrosine ligase like 3) Enables protein-glycine ligase activity. Predicted to be involved in axoneme assembly and flagellated sperm motility. Predicted to be located in axoneme; microtubule cytoskeleton; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

TTLL3 links:

ARPC4-TTLL3 (HGNC:38830): (ARPC4-TTLL3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ARPC4 (actin related protein 2/3 complex, subunit 4) and TTLL3 (tubulin tyrosine ligase-like family, member 3) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ARPC4-TTLL3 links:

TTLL3 (HGNC:):

TTLL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.084762424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL3	NM_001387446.1 linkuse as main transcript	c.-170C>G		5_prime_UTR_variant	1/14	ENST00000685419.1	NP_001374375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL3	ENST00000685419 linkuse as main transcript	c.-170C>G		5_prime_UTR_variant	1/14		NM_001387446.1	ENSP00000510679.1		A0A8I5KXU2
ARPC4-TTLL3	ENST00000397256.5 linkuse as main transcript	c.331-2677C>G		intron_variant		5		ENSP00000380427.1		A0A0A6YYG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000981

AC:

AN:

101928

Hom.:

AF XY:

0.00

AC XY:

AN XY:

57016

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1355526

Hom.:

Cov.:

AF XY:

0.0000464

AC XY:

AN XY:

668636

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:

0.0000589

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.260C>G (p.P87R) alteration is located in exon 1 (coding exon 1) of the TTLL3 gene. This alteration results from a C to G substitution at nucleotide position 260, causing the proline (P) at amino acid position 87 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.0

DANN

Benign

0.65

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.37

M_CAP

Benign

0.028

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

REVEL

Benign

0.010

Sift

Benign

0.050

Sift4G

Uncertain

0.042

Vest4

0.058

MutPred

0.26

Gain of MoRF binding (P = 0.0018);

MVP

0.21

MPC

0.33

ClinPred

0.25

GERP RS

2.3

gMVP

0.047

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