Genetic Variant TTLL8:p.Asp345Asp (chr22-50034409-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000433387.2(TTLL8):c.1035C>T(p.Asp345Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,367,264 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 41 hom. )

Consequence

TTLL8
ENST00000433387.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

Publications

3 publications found

Variant links:

Genes affected

TTLL8 (HGNC:34000): (tubulin tyrosine ligase like 8) Predicted to enable protein-glycine ligase activity, initiating. Predicted to be involved in protein polyglycylation. Predicted to act upstream of or within cilium assembly. Predicted to be located in axoneme and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

TTLL8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 22-50034409-G-A is Benign according to our data. Variant chr22-50034409-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653361.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
TTLL8	NM_001350317.3 link	c.1035C>T	p.Asp345Asp	synonymous_variant	Exon 10 of 14	NP_001337246.1
TTLL8	XM_024452172.1 link	c.1035C>T	p.Asp345Asp	synonymous_variant	Exon 10 of 14	XP_024307940.1
TTLL8	XM_024452173.1 link	c.1032C>T	p.Asp344Asp	synonymous_variant	Exon 10 of 14	XP_024307941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL8	ENST00000433387.2 link	c.1035C>T	p.Asp345Asp	synonymous_variant	Exon 10 of 14	5		ENSP00000392252.2		A0A1C7CYW9

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

981

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00927

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00665

AC:

1653

AN:

248416

AF XY:

0.00677

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.0000998

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.00867

Gnomad OTH exome

AF:

0.00531

GnomAD4 exome

AF:

0.00751

AC:

9122

AN:

1214946

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

4563

AN XY:

602096

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

26300

American (AMR)

AF:

0.00156

AC:

AN:

37284

Ashkenazi Jewish (ASJ)

AF:

0.000118

AC:

AN:

16894

East Asian (EAS)

AF:

0.0000595

AC:

AN:

16806

South Asian (SAS)

AF:

0.00330

AC:

275

AN:

83222

European-Finnish (FIN)

AF:

0.0217

AC:

699

AN:

32188

Middle Eastern (MID)

AF:

0.00269

AC:

AN:

4468

European-Non Finnish (NFE)

AF:

0.00812

AC:

7743

AN:

953790

Other (OTH)

AF:

0.00675

AC:

297

AN:

43994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

479

959

1438

1918

2397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00644

AC:

981

AN:

152318

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

498

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41560

American (AMR)

AF:

0.00150

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0236

AC:

251

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00928

AC:

631

AN:

68032

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

112

168

224

280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00869

Hom.:

Bravo

AF:

0.00456

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TTLL8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.6

(source)

DANN

Benign

0.54

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr22-50034409-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over