dbSNP rs9879307: TTLL3:c.1248-579C>T (chr3-9828381-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387446.1(TTLL3):c.1248-579C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,256 control chromosomes in the GnomAD database, including 32,147 homozygotes. 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: 𝑓 0.64 ( 32089 hom., cov: 32)

Exomes 𝑓: 0.70 ( 58 hom. )

Consequence

TTLL3
NM_001387446.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.356

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387446.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTLL3	NM_001387446.1	MANE Select	c.1248-579C>T	intron	N/A	NP_001374375.1	A0A8I5KXU2
TTLL3	NM_001025930.5		c.1548-579C>T	intron	N/A	NP_001021100.3	J3KQB2
TTLL3	NM_001366051.2		c.1119-579C>T	intron	N/A	NP_001352980.1	Q9Y4R7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTLL3	ENST00000685419.1	MANE Select	c.1248-579C>T	intron	N/A	ENSP00000510679.1	A0A8I5KXU2
ARPC4-TTLL3	ENST00000397256.5	TSL:5	c.1302-579C>T	intron	N/A	ENSP00000380427.1
TTLL3	ENST00000310252.11	TSL:1	c.984-579C>T	intron	N/A	ENSP00000312148.7	H3BLT7

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97187

AN:

151904

Hom.:

32067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.819

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.649

GnomAD4 exome

AF:

0.701

AC:

164

AN:

234

Hom.:

Cov.:

AF XY:

0.663

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.563

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.720

AC:

144

AN:

200

Other (OTH)

AF:

0.700

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.640

AC:

97247

AN:

152022

Hom.:

32089

Cov.:

AF XY:

0.637

AC XY:

47324

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.603

AC:

24994

AN:

41428

American (AMR)

AF:

0.541

AC:

8266

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2497

AN:

3472

East Asian (EAS)

AF:

0.200

AC:

1034

AN:

5174

South Asian (SAS)

AF:

0.445

AC:

2146

AN:

4826

European-Finnish (FIN)

AF:

0.765

AC:

8075

AN:

10560

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.705

AC:

47940

AN:

67970

Other (OTH)

AF:

0.653

AC:

1377

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1700

3400

5099

6799

8499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.680

Hom.:

18199

Bravo

AF:

0.620

Asia WGS

AF:

0.389

AC:

1354

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

-0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over