Variant rs1132079 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_012263.5(TTLL1):c.750G>A(p.Glu250Glu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,611,020 control chromosomes in the GnomAD database, including 61,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4466 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57237 hom. )

Consequence

TTLL1
NM_012263.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0880

Variant links:

Genes affected

TTLL1 (HGNC:1312): (TTL family tubulin polyglutamylase complex subunit L1) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to act upstream of or within several processes, including cerebellar Purkinje cell differentiation; mucociliary clearance; and regulation of blastocyst development. Predicted to be located in cytoplasm; extracellular region; and microtubule cytoskeleton. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

TTLL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 22-43059525-C-T is Benign according to our data. Variant chr22-43059525-C-T is described in ClinVar as [Benign]. Clinvar id is 403579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTLL1	NM_012263.5 link	c.750G>A	p.Glu250Glu	splice_region_variant, synonymous_variant	Exon 8 of 11	ENST00000266254.12	NP_036395.1	O95922-1A0A024R4U6
TTLL1	NR_027779.2 link	n.1058G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 9 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTLL1	ENST00000266254.12 link	c.750G>A	p.Glu250Glu	splice_region_variant, synonymous_variant	Exon 8 of 11	1	NM_012263.5	ENSP00000266254.7		O95922-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33962

AN:

151946

Hom.:

4464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.00462

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.251

AC:

61642

AN:

246058

Hom.:

8810

AF XY:

0.257

AC XY:

34119

AN XY:

132996

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.00115

Gnomad SAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.272

AC:

397544

AN:

1458954

Hom.:

57237

Cov.:

AF XY:

0.274

AC XY:

198635

AN XY:

725610

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.000959

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.223

AC:

33971

AN:

152066

Hom.:

4466

Cov.:

AF XY:

0.221

AC XY:

16448

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.00463

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.278

Hom.:

8955

Bravo

AF:

0.220

Asia WGS

AF:

0.118

AC:

412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.1

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.38

Position offset: -2

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