3-39110988-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366900.1(TTC21A):ā€‹c.406A>Gā€‹(p.Met136Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

TTC21A
NM_001366900.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86
Variant links:
Genes affected
TTC21A (HGNC:30761): (tetratricopeptide repeat domain 21A) Involved in flagellated sperm motility and spermatid development. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle A. Implicated in spermatogenic failure 37. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17308298).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TTC21ANM_001366900.1 linkuse as main transcriptc.406A>G p.Met136Val missense_variant 4/29 ENST00000683103.1 NP_001353829.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TTC21AENST00000683103.1 linkuse as main transcriptc.406A>G p.Met136Val missense_variant 4/29 NM_001366900.1 ENSP00000507739 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248166
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134760
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1459838
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
725994
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 01, 2022The c.406A>G (p.M136V) alteration is located in exon 4 (coding exon 4) of the TTC21A gene. This alteration results from a A to G substitution at nucleotide position 406, causing the methionine (M) at amino acid position 136 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
11
DANN
Benign
0.63
DEOGEN2
Benign
0.016
T;.
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.54
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.0
M;M
MutationTaster
Benign
0.97
N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.078
Sift
Benign
0.063
T;T
Sift4G
Benign
0.065
T;T
Polyphen
0.049
B;B
Vest4
0.19
MutPred
0.41
Loss of glycosylation at K138 (P = 0.0553);Loss of glycosylation at K138 (P = 0.0553);
MVP
0.67
MPC
0.14
ClinPred
0.10
T
GERP RS
2.0
Varity_R
0.16
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs754402212; hg19: chr3-39152479; API