ENST00000397256.5:c.331-2819C>T

Variant names:

• chr3-9810124-C-T
• rs1006114674
• ENST00000397256.5:c.331-2819C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000397256.5(ARPC4-TTLL3):​c.331-2819C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,317,494 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ARPC4-TTLL3 ENST00000397256.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

Genes affected

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]

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]

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=0.08213949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL3	NM_001387446.1	c.-312C>T		upstream_gene_variant		ENST00000685419.1	NP_001374375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC4-TTLL3	ENST00000397256.5	c.331-2819C>T		intron_variant	Intron 4 of 11	5		ENSP00000380427.1
TTLL3	ENST00000685419.1	c.-312C>T		upstream_gene_variant			NM_001387446.1	ENSP00000510679.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1317494 Hom.: 0 Cov.: 71 AF XY: 0.00000154 AC XY: 1 AN XY: 648748

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: 0.00000190

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	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.1
DANN	Benign	0.95
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.037
Sift	Benign	0.25	T
Sift4G	Benign	0.41	T
Vest4		0.046
MutPred		0.18		Loss of relative solvent accessibility (P = 0.0071);
MVP		0.30
MPC		0.093
ClinPred		0.073	T
GERP RS		1.2
gMVP		0.13

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: rs1006114674; hg19: chr3-9851808;