3-9819196-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000383827.5(TTLL3):​c.-1457G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 465,906 control chromosomes in the GnomAD database, including 176,285 homozygotes. 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: 𝑓 0.87 (57604 hom., cov: 29)
  • Exomes 𝑓: 0.87 (118681 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131994 AN: 151846 Hom.: 57564 Cov.: 29

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.860

GnomAD4 exome AF: 0.867 AC: 272107 AN: 313944 Hom.: 118681 Cov.: 4 AF XY: 0.862 AC XY: 142319 AN XY: 165100

African (AFR) AF: 0.876 AC: 8168 AN: 9328

American (AMR) AF: 0.739 AC: 9516 AN: 12878

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 8342 AN: 9542

East Asian (EAS) AF: 0.717 AC: 14535 AN: 20262

South Asian (SAS) AF: 0.792 AC: 27741 AN: 35020

European-Finnish (FIN) AF: 0.941 AC: 18105 AN: 19248

Middle Eastern (MID) AF: 0.890 AC: 1243 AN: 1396

European-Non Finnish (NFE) AF: 0.896 AC: 168709 AN: 188220

Other (OTH) AF: 0.872 AC: 15748 AN: 18050

GnomAD4 genome AF: 0.869 AC: 132085 AN: 151962 Hom.: 57604 Cov.: 29 AF XY: 0.867 AC XY: 64394 AN XY: 74292

African (AFR) AF: 0.872 AC: 36113 AN: 41434

American (AMR) AF: 0.769 AC: 11720 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3024 AN: 3468

East Asian (EAS) AF: 0.756 AC: 3884 AN: 5136

South Asian (SAS) AF: 0.783 AC: 3769 AN: 4812

European-Finnish (FIN) AF: 0.943 AC: 9985 AN: 10586

Middle Eastern (MID) AF: 0.897 AC: 262 AN: 292

European-Non Finnish (NFE) AF: 0.892 AC: 60637 AN: 67982

Other (OTH) AF: 0.861 AC: 1810 AN: 2102

Alfa AF: 0.882 Hom.: 94983

Bravo AF: 0.859

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.32
PromoterAI		0.0013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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;