Variant 22-43051885-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_012263.5(TTLL1):c.894G>A(p.Pro298=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,613,604 control chromosomes in the GnomAD database, including 1,898 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 127 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1771 hom. )

Consequence

TTLL1
NM_012263.5 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61

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:

TTLL1-AS1 (HGNC:40111): (TTLL1 antisense RNA 1)

TTLL1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 22-43051885-C-T is Benign according to our data. Variant chr22-43051885-C-T is described in ClinVar as [Benign]. Clinvar id is 403577.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TTLL1	NM_012263.5 linkuse as main transcript	c.894G>A	p.Pro298=	splice_region_variant, synonymous_variant	9/11	ENST00000266254.12
TTLL1-AS1	NR_125362.1 linkuse as main transcript	n.1772-170C>T		intron_variant, non_coding_transcript_variant
TTLL1	NR_027779.2 linkuse as main transcript	n.1202G>A		splice_region_variant, non_coding_transcript_exon_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTLL1	ENST00000266254.12 linkuse as main transcript	c.894G>A	p.Pro298=	splice_region_variant, synonymous_variant	9/11	1	NM_012263.5	P1	O95922-1
TTLL1-AS1	ENST00000443063.1 linkuse as main transcript	n.1772-170C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5029

AN:

151978

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00978

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0274

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.0564

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0274

GnomAD3 exomes

AF:

0.0335

AC:

8416

AN:

251380

Hom.:

211

AF XY:

0.0341

AC XY:

4639

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00954

Gnomad AMR exome

AF:

0.0178

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0503

Gnomad OTH exome

AF:

0.0360

GnomAD4 exome

AF:

0.0460

AC:

67294

AN:

1461508

Hom.:

1771

Cov.:

AF XY:

0.0449

AC XY:

32651

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00842

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0539

Gnomad4 NFE exome

AF:

0.0532

Gnomad4 OTH exome

AF:

0.0404

GnomAD4 genome

AF:

0.0331

AC:

5028

AN:

152096

Hom.:

127

Cov.:

AF XY:

0.0327

AC XY:

2430

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00973

Gnomad4 AMR

AF:

0.0274

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.0564

Gnomad4 NFE

AF:

0.0498

Gnomad4 OTH

AF:

0.0271

Alfa

AF:

0.0385

Hom.:

Bravo

AF:

0.0297

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0457

EpiControl

AF:

0.0462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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, silent -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.87

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.87

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