chr3-39114630-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366900.1(TTC21A):​c.604G>A​(p.Val202Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,614,072 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 (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

TTC21A
NM_001366900.1 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.041511804).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TTC21ANM_001366900.1 linkuse as main transcriptc.604G>A p.Val202Met missense_variant 6/29 ENST00000683103.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TTC21AENST00000683103.1 linkuse as main transcriptc.604G>A p.Val202Met missense_variant 6/29 NM_001366900.1 P1

Frequencies

GnomAD3 genomes
AF:
0.000315
AC:
48
AN:
152198
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00104
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.0000962
AC:
24
AN:
249460
Hom.:
0
AF XY:
0.0000591
AC XY:
8
AN XY:
135326
show subpopulations
Gnomad AFR exome
AF:
0.000969
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000328
AC:
48
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000836
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000315
AC:
48
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.000256
AC XY:
19
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00104
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000956
Alfa
AF:
0.000267
Hom.:
0
Bravo
AF:
0.000400
ESP6500AA
AF:
0.000247
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsJun 10, 2022The c.604G>A (p.V202M) alteration is located in exon 6 (coding exon 6) of the TTC21A gene. This alteration results from a G to A substitution at nucleotide position 604, causing the valine (V) at amino acid position 202 to be replaced by a methionine (M). 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
0.098
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T;.
Eigen
Benign
-0.084
Eigen_PC
Benign
-0.027
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.042
T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
2.0
M;.
MutationTaster
Benign
0.62
N;N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.055
Sift
Benign
0.048
D;D
Sift4G
Uncertain
0.052
T;T
Polyphen
0.45
B;P
Vest4
0.23
MVP
0.76
MPC
0.16
ClinPred
0.012
T
GERP RS
3.1
Varity_R
0.099
gMVP
0.17

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: rs35876903; hg19: chr3-39156121; API