X-80443597-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_152630.5(TENT5D):c.1058C>T(p.Pro353Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,208,585 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000046 ( 0 hom. 20 hem. )
Consequence
TENT5D
NM_152630.5 missense
NM_152630.5 missense
Scores
3
9
4
Clinical Significance
Conservation
PhyloP100: 7.31
Genes affected
TENT5D (HGNC:28399): (terminal nucleotidyltransferase 5D) Antibodies against the protein encoded by this gene were found only in plasma from cancer patients. While it may be a target for immunotherapy, the function of this gene is unknown. [provided by RefSeq, Dec 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.82
BS2
?
High Hemizygotes in GnomAdExome at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TENT5D | NM_152630.5 | c.1058C>T | p.Pro353Leu | missense_variant | 3/3 | ENST00000308293.6 | |
TENT5D | NM_001170574.2 | c.1058C>T | p.Pro353Leu | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TENT5D | ENST00000308293.6 | c.1058C>T | p.Pro353Leu | missense_variant | 3/3 | 1 | NM_152630.5 | P1 | |
TENT5D | ENST00000538312.5 | c.1058C>T | p.Pro353Leu | missense_variant | 5/5 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000898 AC: 1AN: 111389Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33681
GnomAD3 genomes
?
AF:
AC:
1
AN:
111389
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
33681
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000164 AC: 3AN: 182474Hom.: 0 AF XY: 0.0000297 AC XY: 2AN XY: 67276
GnomAD3 exomes
AF:
AC:
3
AN:
182474
Hom.:
AF XY:
AC XY:
2
AN XY:
67276
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000456 AC: 50AN: 1097196Hom.: 0 Cov.: 32 AF XY: 0.0000551 AC XY: 20AN XY: 362868
GnomAD4 exome
AF:
AC:
50
AN:
1097196
Hom.:
Cov.:
32
AF XY:
AC XY:
20
AN XY:
362868
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000898 AC: 1AN: 111389Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33681
GnomAD4 genome
?
AF:
AC:
1
AN:
111389
Hom.:
Cov.:
23
AF XY:
AC XY:
0
AN XY:
33681
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ExAC
?
AF:
AC:
2
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 submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.1058C>T (p.P353L) alteration is located in exon 5 (coding exon 1) of the FAM46D gene. This alteration results from a C to T substitution at nucleotide position 1058, causing the proline (P) at amino acid position 353 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at P353 (P = 0.0099);Loss of catalytic residue at P353 (P = 0.0099);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at