dbSNP rs1208158519: TTLL3:c.-171C>G (chr3-9810265-C-G) – 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 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P87S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

TTLL3
NM_001025930.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.116

Publications

0 publications found

Variant links:

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]

TTLL3 links:

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:

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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=0.07667518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025930.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTLL3	NM_001387446.1	MANE Select	c.-171C>G		5_prime_UTR	Exon 1 of 14	NP_001374375.1	A0A8I5KXU2
TTLL3	NM_001025930.5		c.259C>G	p.Pro87Ala	missense	Exon 1 of 13	NP_001021100.3	J3KQB2
TTLL3	NM_001366051.2		c.-171C>G		5_prime_UTR	Exon 1 of 13	NP_001352980.1	Q9Y4R7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTLL3	ENST00000685419.1	MANE Select	c.-171C>G	5_prime_UTR	Exon 1 of 14	ENSP00000510679.1	A0A8I5KXU2
ARPC4-TTLL3	ENST00000397256.5	TSL:5	c.331-2678C>G	intron	N/A	ENSP00000380427.1
TTLL3	ENST00000427220.5	TSL:1	n.-397C>G	non_coding_transcript_exon	Exon 1 of 11	ENSP00000395912.1	F8WD18

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.38e-7

AC:

AN:

1355236

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

668468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27942

American (AMR)

AF:

0.00

AC:

AN:

32154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23988

East Asian (EAS)

AF:

0.00

AC:

AN:

32192

South Asian (SAS)

AF:

0.00

AC:

AN:

76404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4046

European-Non Finnish (NFE)

AF:

9.36e-7

AC:

AN:

1068838

Other (OTH)

AF:

0.00

AC:

AN:

56518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.3

(source)

DANN

Benign

0.88

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.39

M_CAP

Benign

0.048

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.90

PhyloP100

-0.12

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.6

REVEL

Benign

0.037

Sift

Benign

0.31

Sift4G

Benign

0.51

Vest4

0.11

MutPred

0.12

Loss of glycosylation at P89 (P = 0.0196)

MVP

0.17

MPC

0.15

ClinPred

0.099

GERP RS

2.4

PromoterAI

-0.24

Neutral

(source)

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

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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