ENST00000383827.5:c.-1457G>C

Variant names:

• chr3-9819196-G-C
• rs3806667
• ENST00000383827.5:c.-1457G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000383827.5(TTLL3):​c.-1457G>C variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTLL3 ENST00000383827.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL3	NM_001387446.1	c.658+276G>C		intron_variant	Intron 7 of 13	ENST00000685419.1	NP_001374375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL3	ENST00000685419.1	c.658+276G>C		intron_variant	Intron 7 of 13		NM_001387446.1	ENSP00000510679.1
ARPC4-TTLL3	ENST00000397256.5	c.713-1350G>C		intron_variant	Intron 7 of 11	5		ENSP00000380427.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 314386 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 165328

African (AFR) AF: 0.00 AC: 0 AN: 9346

American (AMR) AF: 0.00 AC: 0 AN: 12904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9554

East Asian (EAS) AF: 0.00 AC: 0 AN: 20322

South Asian (SAS) AF: 0.00 AC: 0 AN: 35084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1398

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 188444

Other (OTH) AF: 0.00 AC: 0 AN: 18074

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 94983

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.32
PromoterAI		0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs3806667; hg19: chr3-9860880;