1-28571871-A-T

Variant summary

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

The ENST00000373830.4(TRNAU1AP):​c.698A>T​(p.Tyr233Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000257 in 1,613,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

TRNAU1AP
ENST00000373830.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15
Variant links:
Genes affected
TRNAU1AP (HGNC:30813): (tRNA selenocysteine 1 associated protein 1) Enables RNA binding activity. Predicted to be involved in selenocysteine incorporation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [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=0.10880789).
BS2
High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRNAU1APNM_017846.5 linkuse as main transcriptc.698A>T p.Tyr233Phe missense_variant 8/9 ENST00000373830.4 NP_060316.1
TRNAU1APNR_003109.2 linkuse as main transcriptn.872A>T non_coding_transcript_exon_variant 9/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRNAU1APENST00000373830.4 linkuse as main transcriptc.698A>T p.Tyr233Phe missense_variant 8/91 NM_017846.5 ENSP00000362936 P1Q9NX07-1
TRNAU1APENST00000480930.5 linkuse as main transcriptn.858A>T non_coding_transcript_exon_variant 9/101
TRNAU1APENST00000484775.1 linkuse as main transcriptn.573A>T non_coding_transcript_exon_variant 6/85
TRNAU1APENST00000491577.5 linkuse as main transcriptn.1316A>T non_coding_transcript_exon_variant 7/82

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
151834
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000280
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251472
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135908
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:
0.000105
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000270
AC:
395
AN:
1461448
Hom.:
0
Cov.:
30
AF XY:
0.000261
AC XY:
190
AN XY:
727060
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:
0.000354
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
151952
Hom.:
0
Cov.:
30
AF XY:
0.000121
AC XY:
9
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000280
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000188
Hom.:
0
Bravo
AF:
0.000117
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
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 GeneticsOct 30, 2023The c.698A>T (p.Y233F) alteration is located in exon 8 (coding exon 8) of the TRNAU1AP gene. This alteration results from a A to T substitution at nucleotide position 698, causing the tyrosine (Y) at amino acid position 233 to be replaced by a phenylalanine (F). 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
0.086
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
21
DANN
Benign
0.93
DEOGEN2
Benign
0.049
T
Eigen
Uncertain
0.22
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.058
Sift
Benign
0.43
T
Sift4G
Benign
0.62
T
Polyphen
0.65
P
Vest4
0.51
MVP
0.093
MPC
0.74
ClinPred
0.22
T
GERP RS
5.6
Varity_R
0.12
gMVP
0.44

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: rs150193045; hg19: chr1-28898383; API