6-44282504-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_182539.4(TCTE1):​c.902G>A​(p.Arg301Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000089 in 1,606,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

TCTE1
NM_182539.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.518
Variant links:
Genes affected
TCTE1 (HGNC:11693): (t-complex-associated-testis-expressed 1) Predicted to be involved in flagellated sperm motility. Predicted to be located in sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]
TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.097952515).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TCTE1NM_182539.4 linkc.902G>A p.Arg301Gln missense_variant Exon 4 of 5 ENST00000371505.5 NP_872345.2 Q5JU00

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TCTE1ENST00000371505.5 linkc.902G>A p.Arg301Gln missense_variant Exon 4 of 5 1 NM_182539.4 ENSP00000360560.4 Q5JU00
ENSG00000272442ENST00000505802.1 linkn.312+8998C>T intron_variant Intron 1 of 9 2 ENSP00000424257.1 H0Y9J4
TMEM151BENST00000438774.2 linkc.576+8998C>T intron_variant Intron 2 of 2 3 ENSP00000409337.2 Q8IW70-2
TCTE1ENST00000371504.1 linkc.388-2114G>A intron_variant Intron 1 of 1 3 ENSP00000360559.1 Q5JU01

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000613
AC:
15
AN:
244832
Hom.:
0
AF XY:
0.0000829
AC XY:
11
AN XY:
132724
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000797
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000949
AC:
138
AN:
1454320
Hom.:
0
Cov.:
35
AF XY:
0.000104
AC XY:
75
AN XY:
723714
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:
0.000197
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000105
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000659
AC:
8
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
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.902G>A (p.R301Q) alteration is located in exon 4 (coding exon 3) of the TCTE1 gene. This alteration results from a G to A substitution at nucleotide position 902, causing the arginine (R) at amino acid position 301 to be replaced by a glutamine (Q). 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
0.10
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0049
T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.78
N
REVEL
Benign
0.072
Sift
Benign
0.25
T
Sift4G
Benign
0.25
T
Polyphen
0.92
P
Vest4
0.36
MutPred
0.38
Loss of MoRF binding (P = 0.0544);
MVP
0.048
MPC
0.63
ClinPred
0.18
T
GERP RS
3.6
Varity_R
0.098
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs369127426; hg19: chr6-44250241; COSMIC: COSV101025461; COSMIC: COSV101025461; API