rs9879307

chr3-9828381-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387446.1(TTLL3):c.1248-579C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,256 control chromosomes in the GnomAD database, including 32,147 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 0.64 (32089 hom., cov: 32)
  • Exomes 𝑓: 0.70 (58 hom.)
• Consequence: TTLL3 NM_001387446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTLL3	NM_001387446.1	c.1248-579C>T		intron_variant		ENST00000685419.1
ARPC4-TTLL3	NM_001198793.1	c.1302-579C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL3	ENST00000685419.1	c.1248-579C>T		intron_variant			NM_001387446.1	A2

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97187 AN: 151904 Hom.: 32067 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.701 AC: 164 AN: 234 Hom.: 58 Cov.: 0 AF XY: 0.663 AC XY: 65 AN XY: 98

Gnomad4 AMR exome AF: 0.563

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.640 AC: 97247 AN: 152022 Hom.: 32089 Cov.: 32 AF XY: 0.637 AC XY: 47324 AN XY: 74302

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.653

Alfa AF: 0.679 Hom.: 16198

Bravo AF: 0.620

Asia WGS AF: 0.389 AC: 1354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	11
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs9879307; hg19: chr3-9870065;