Variant 22-50034409-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001350317.3(TTLL8):c.1035C>T(p.Asp345=) 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
NM_001350317.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTLL8	NM_001350317.3 linkuse as main transcript	c.1035C>T	p.Asp345=	synonymous_variant	10/14	ENST00000433387.2	NP_001337246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTLL8	ENST00000433387.2 linkuse as main transcript	c.1035C>T	p.Asp345=	synonymous_variant	10/14	5	NM_001350317.3	ENSP00000392252	P1

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

GnomAD3 exomes

AF:

0.00665

AC:

1653

AN:

248416

Hom.:

AF XY:

0.00677

AC XY:

914

AN XY:

135076

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 SAS exome

AF:

0.00347

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

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.0000595

Gnomad4 SAS exome

AF:

0.00330

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.00812

Gnomad4 OTH exome

AF:

0.00675

GnomAD4 genome

AF:

0.00644

AC:

981

AN:

152318

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

498

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.00928

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00705

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

TTLL8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.6

DANN

Benign

0.54

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over