chr3-9819196-G-T

Position:

• chr3-9819196-G-T

Variant summary

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

The NM_001387446.1(TTLL3):​c.658+276G>T variant causes a intron 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 NM_001387446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.93).
• 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/exons	MANE	Protein	UniProt
TTLL3	NM_001387446.1	c.658+276G>T		intron_variant		ENST00000685419.1	NP_001374375.1
ARPC4-TTLL3	NM_001198793.1	c.713-1350G>T		intron_variant			NP_001185722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL3	ENST00000685419.1	c.658+276G>T		intron_variant			NM_001387446.1	ENSP00000510679	A2

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

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.739

Gnomad4 ASJ exome AF: 0.874

Gnomad4 EAS exome AF: 0.717

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.941

Gnomad4 NFE exome AF: 0.896

Gnomad4 OTH exome AF: 0.872

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

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.861

Alfa AF: 0.883 Hom.: 75822

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

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

Other links and lift over

dbSNP: rs3806667; hg19: chr3-9860880;