chr18-267971-A-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000261600.11(THOC1):ā€‹c.49T>Gā€‹(p.Phe17Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,611,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

THOC1
ENST00000261600.11 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99
Variant links:
Genes affected
THOC1 (HGNC:19070): (THO complex subunit 1) Predicted to enable DNA binding activity and RNA binding activity. Involved in several processes, including negative regulation of DNA damage checkpoint; regulation of nucleobase-containing compound metabolic process; and viral mRNA export from host cell nucleus. Located in cytoplasm and nuclear speck. Part of THO complex part of transcription export complex. Colocalizes with chromosome, telomeric region. [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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.41647202).
BS2
High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THOC1NM_005131.3 linkuse as main transcriptc.49T>G p.Phe17Val missense_variant 1/21 ENST00000261600.11 NP_005122.2
THOC1XM_011525772.4 linkuse as main transcriptc.49T>G p.Phe17Val missense_variant 1/21 XP_011524074.1
THOC1XM_017026104.2 linkuse as main transcriptc.49T>G p.Phe17Val missense_variant 1/12 XP_016881593.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THOC1ENST00000261600.11 linkuse as main transcriptc.49T>G p.Phe17Val missense_variant 1/211 NM_005131.3 ENSP00000261600 P1Q96FV9-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
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:
0.00
GnomAD3 exomes
AF:
0.0000247
AC:
6
AN:
242748
Hom.:
0
AF XY:
0.0000227
AC XY:
3
AN XY:
132384
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000609
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1459482
Hom.:
0
Cov.:
30
AF XY:
0.0000152
AC XY:
11
AN XY:
725840
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000500
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:
0.0000332
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
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 submitterclinical testingAmbry GeneticsJul 06, 2021The c.49T>G (p.F17V) alteration is located in exon 1 (coding exon 1) of the THOC1 gene. This alteration results from a T to G substitution at nucleotide position 49, causing the phenylalanine (F) at amino acid position 17 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
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
27
DANN
Benign
0.58
DEOGEN2
Benign
0.40
T;.;.
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.42
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
2.0
M;.;.
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Uncertain
-2.6
D;.;.
REVEL
Benign
0.17
Sift
Uncertain
0.0040
D;.;.
Sift4G
Benign
0.084
T;D;T
Polyphen
0.99
D;.;.
Vest4
0.69
MutPred
0.41
Gain of MoRF binding (P = 0.0738);Gain of MoRF binding (P = 0.0738);Gain of MoRF binding (P = 0.0738);
MVP
0.43
MPC
0.84
ClinPred
0.39
T
GERP RS
4.4
Varity_R
0.87
gMVP
0.72

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: rs752304581; hg19: chr18-267971; API