Menu
GeneBe

22-43039806-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_012263.5(TTLL1):c.1242G>A(p.Ser414=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,613,284 control chromosomes in the GnomAD database, including 56,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 9371 hom., cov: 31)
Exomes 𝑓: 0.22 ( 47063 hom. )

Consequence

TTLL1
NM_012263.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78
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-AS1 (HGNC:40111): (TTLL1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-43039806-C-T is Benign according to our data. Variant chr22-43039806-C-T is described in ClinVar as [Benign]. Clinvar id is 403576.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.78 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TTLL1NM_012263.5 linkuse as main transcriptc.1242G>A p.Ser414= synonymous_variant 11/11 ENST00000266254.12
TTLL1-AS1NR_125362.1 linkuse as main transcriptn.1222C>T non_coding_transcript_exon_variant 1/3
TTLL1NR_027779.2 linkuse as main transcriptn.1550G>A non_coding_transcript_exon_variant 12/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTLL1ENST00000266254.12 linkuse as main transcriptc.1242G>A p.Ser414= synonymous_variant 11/111 NM_012263.5 P1O95922-1
TTLL1-AS1ENST00000443063.1 linkuse as main transcriptn.1222C>T non_coding_transcript_exon_variant 1/31

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.306
AC:
46440
AN:
151840
Hom.:
9373
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.479
Gnomad AMI
AF:
0.0912
Gnomad AMR
AF:
0.393
Gnomad ASJ
AF:
0.169
Gnomad EAS
AF:
0.818
Gnomad SAS
AF:
0.371
Gnomad FIN
AF:
0.143
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.173
Gnomad OTH
AF:
0.305
GnomAD3 exomes
AF:
0.300
AC:
75097
AN:
249952
Hom.:
16350
AF XY:
0.288
AC XY:
38979
AN XY:
135376
show subpopulations
Gnomad AFR exome
AF:
0.487
Gnomad AMR exome
AF:
0.457
Gnomad ASJ exome
AF:
0.180
Gnomad EAS exome
AF:
0.842
Gnomad SAS exome
AF:
0.345
Gnomad FIN exome
AF:
0.141
Gnomad NFE exome
AF:
0.171
Gnomad OTH exome
AF:
0.237
GnomAD4 exome
AF:
0.217
AC:
316923
AN:
1461326
Hom.:
47063
Cov.:
32
AF XY:
0.218
AC XY:
158429
AN XY:
726920
show subpopulations
Gnomad4 AFR exome
AF:
0.490
Gnomad4 AMR exome
AF:
0.452
Gnomad4 ASJ exome
AF:
0.176
Gnomad4 EAS exome
AF:
0.804
Gnomad4 SAS exome
AF:
0.337
Gnomad4 FIN exome
AF:
0.140
Gnomad4 NFE exome
AF:
0.172
Gnomad4 OTH exome
AF:
0.257
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.306
AC:
46467
AN:
151958
Hom.:
9371
Cov.:
31
AF XY:
0.311
AC XY:
23079
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.478
Gnomad4 AMR
AF:
0.393
Gnomad4 ASJ
AF:
0.169
Gnomad4 EAS
AF:
0.817
Gnomad4 SAS
AF:
0.368
Gnomad4 FIN
AF:
0.143
Gnomad4 NFE
AF:
0.173
Gnomad4 OTH
AF:
0.304
Alfa
AF:
0.221
Hom.:
1994
Bravo
AF:
0.335
Asia WGS
AF:
0.555
AC:
1929
AN:
3478
EpiCase
AF:
0.172
EpiControl
AF:
0.177

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
Cadd
Benign
0.47
Dann
Benign
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs1052163; hg19: chr22-43435812; COSMIC: COSV56737879; API