chr3-9810283-C-T

Position:

• chr3-9810283-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025930.5(TTLL3):​c.277C>T​(p.Leu93Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TTLL3 NM_001025930.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.966

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]

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]

TTLL3 (HGNC:):

ACMG classification

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=0.0974313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL3	NM_001387446.1	c.-153C>T		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	c.-153C>T		5_prime_UTR_variant	1/14		NM_001387446.1	ENSP00000510679.1
ARPC4-TTLL3	ENST00000397256.5	c.331-2660C>T		intron_variant		5		ENSP00000380427.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.277C>T (p.L93F) alteration is located in exon 1 (coding exon 1) of the TTLL3 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the leucine (L) at amino acid position 93 to be replaced by a phenylalanine (F). 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	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Uncertain	0.98
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.046
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Vest4		0.055
MutPred		0.15		Loss of glycosylation at P89 (P = 0.0196);
MVP		0.16
MPC		0.50
ClinPred		0.33	T
GERP RS		2.3
gMVP		0.049

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: chr3-9851967;