Genetic Variant ENST00000397256.5:c.331-2819C>T (chr3-9810124-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.382

Publications

0 publications found

Variant links:

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]

ARPC4-TTLL3 links:

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]

TTLL3 links:

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ACMG classification

Classification was made for transcript

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=0.08213949).

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

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTLL3	NM_001025930.5	c.118C>T	p.Pro40Ser	missense	Exon 1 of 13	NP_001021100.3	J3KQB2
TTLL3	NM_001387448.1	c.-42+202C>T		intron	N/A	NP_001374377.1
ARPC4-TTLL3	NM_001198793.1	c.331-2819C>T		intron	N/A	NP_001185722.1	A0A0A6YYG9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ARPC4-TTLL3	ENST00000397256.5	TSL:5	c.331-2819C>T	intron	N/A	ENSP00000380427.1
TTLL3	ENST00000427220.5	TSL:1	n.-538C>T	non_coding_transcript_exon	Exon 1 of 11	ENSP00000395912.1	F8WD18
TTLL3	ENST00000427220.5	TSL:1	n.-538C>T	5_prime_UTR	Exon 1 of 11	ENSP00000395912.1	F8WD18

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1317494

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

648748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26558

American (AMR)

AF:

0.00

AC:

AN:

24808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23188

East Asian (EAS)

AF:

0.00

AC:

AN:

28604

South Asian (SAS)

AF:

0.00

AC:

AN:

72424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4152

European-Non Finnish (NFE)

AF:

0.00000190

AC:

AN:

1050276

Other (OTH)

AF:

0.00

AC:

AN:

54754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.1

(source)

DANN

Benign

0.95

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.38

M_CAP

Benign

0.030

MetaRNN

Benign

0.082

MetaSVM

Benign

-0.92

PhyloP100

0.38

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.87

REVEL

Benign

0.037

Sift

Benign

0.25

Sift4G

Benign

0.41

Vest4

0.046

MutPred

0.18

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.30

MPC

0.093

ClinPred

0.073

GERP RS

1.2

PromoterAI

0.11

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over