X-123614070-GTCCTTT-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_001081550.2(THOC2):​c.4425_4430delAAAGGA​(p.Glu1475_Lys1476del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000275 in 1,091,619 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

THOC2
NM_001081550.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
THOC2 (HGNC:19073): (THO complex subunit 2) The TREX multiprotein complex binds specifically to spliced mRNAs to facilitate mRNA export. The protein encoded by this gene is a member of the THO complex, a subset of the TREX complex. The encoded protein interacts with the THOC1 protein.[provided by RefSeq, Jun 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001081550.2.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
THOC2NM_001081550.2 linkc.4425_4430delAAAGGA p.Glu1475_Lys1476del disruptive_inframe_deletion 34/39 ENST00000245838.13 NP_001075019.1 Q8NI27-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
THOC2ENST00000245838.13 linkc.4425_4430delAAAGGA p.Glu1475_Lys1476del disruptive_inframe_deletion 34/395 NM_001081550.2 ENSP00000245838.8 Q8NI27-1
THOC2ENST00000355725.8 linkc.4425_4430delAAAGGA p.Glu1475_Lys1476del disruptive_inframe_deletion 34/395 ENSP00000347959.4 Q8NI27-1
THOC2ENST00000491737.5 linkc.4080_4085delAAAGGA p.Glu1360_Lys1361del disruptive_inframe_deletion 30/345 ENSP00000419795.1 A0A0C4DG98
THOC2ENST00000441692.5 linkc.807_812delAAAGGA p.Glu269_Lys270del disruptive_inframe_deletion 5/105 ENSP00000415211.1 H0Y7U4
THOC2ENST00000448128.5 linkc.210_215delAAAGGA p.Glu70_Lys71del disruptive_inframe_deletion 4/95 ENSP00000397317.1 H0Y594
THOC2ENST00000416618.5 linkc.192_197delAAAGGA p.Glu64_Lys65del disruptive_inframe_deletion 3/85 ENSP00000415244.1 B7ZBA0
THOC2ENST00000432353.5 linkn.*667_*672delAAAGGA non_coding_transcript_exon_variant 4/91 ENSP00000415947.1 H7C477
THOC2ENST00000432353.5 linkn.*667_*672delAAAGGA 3_prime_UTR_variant 4/91 ENSP00000415947.1 H7C477

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000275
AC:
3
AN:
1091619
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
359101
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000996
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMay 22, 2023Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs759270626; hg19: chrX-122747921; API