ENST00000397256.5:c.331-2866C>T

Variant names:

• chr3-9810077-C-T
• rs776950654
• ENST00000397256.5:c.331-2866C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000397256.5(ARPC4-TTLL3):​c.331-2866C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,238,554 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: 8.1e-7 (0 hom.)
• Consequence: ARPC4-TTLL3 ENST00000397256.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17354071).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397256.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL3	NM_001025930.5		c.71C>T	p.Ser24Phe	missense	Exon 1 of 13	NP_001021100.3	J3KQB2
	TTLL3	NM_001387448.1		c.-42+155C>T		intron	N/A	NP_001374377.1
	ARPC4-TTLL3	NM_001198793.1		c.331-2866C>T		intron	N/A	NP_001185722.1	A0A0A6YYG9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC4-TTLL3	ENST00000397256.5	TSL:5	c.331-2866C>T		intron	N/A	ENSP00000380427.1
	TTLL3	ENST00000427220.5	TSL:1	n.-585C>T		non_coding_transcript_exon	Exon 1 of 11	ENSP00000395912.1	F8WD18
	TTLL3	ENST00000427220.5	TSL:1	n.-585C>T		5_prime_UTR	Exon 1 of 11	ENSP00000395912.1	F8WD18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000329 AC: 1 AN: 30382 AF XY: 0.0000537

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1238554 Hom.: 0 Cov.: 70 AF XY: 0.00000166 AC XY: 1 AN XY: 604186

African (AFR) AF: 0.00 AC: 0 AN: 24068

American (AMR) AF: 0.00 AC: 0 AN: 13636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.00 AC: 0 AN: 27290

South Asian (SAS) AF: 0.0000167 AC: 1 AN: 59996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1009328

Other (OTH) AF: 0.00 AC: 0 AN: 50806

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000818 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Uncertain	0.98
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.50	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.2	T
PhyloP100		0.27
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.031
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Vest4		0.13
MutPred		0.43		Gain of glycosylation at S22 (P = 0.0086)
MVP		0.23
MPC		0.13
ClinPred		0.52	D
GERP RS		3.7
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs776950654; hg19: chr3-9851761;