rs1208158519

Variant names:

• chr3-9810265-C-G
• NM_001387446.1:c.-171C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-9810265-C-G
• chr3-9810265-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.259C>G​(p.Pro87Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000738 in 1,355,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict 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: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TTLL3 NM_001025930.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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

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=0.07667518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL3	NM_001387446.1	c.-171C>G		5_prime_UTR_variant	Exon 1 of 14	ENST00000685419.1	NP_001374375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL3	ENST00000685419	c.-171C>G		5_prime_UTR_variant	Exon 1 of 14		NM_001387446.1	ENSP00000510679.1
ARPC4-TTLL3	ENST00000397256.5	c.331-2678C>G		intron_variant	Intron 4 of 11	5		ENSP00000380427.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.38e-7 AC: 1 AN: 1355236 Hom.: 0 Cov.: 71 AF XY: 0.00000150 AC XY: 1 AN XY: 668468

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.36e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.3
DANN	Benign	0.88
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.90	T
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.037
Sift	Benign	0.31	T
Sift4G	Benign	0.51	T
Vest4		0.11
MutPred		0.12		Loss of glycosylation at P89 (P = 0.0196);
MVP		0.17
MPC		0.15
ClinPred		0.099	T
GERP RS		2.4
gMVP		0.035

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: chr3-9851949;