chr16-3025709-C-A

Variant names:

• chr16-3025709-C-A
• NM_024339.5:c.41C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024339.5(THOC6):​c.41C>A​(p.Thr14Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: THOC6 NM_024339.5 missense, splice_region
• Scores: Splicing: ADA: 0.0001742
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

Genes affected

THOC6 (HGNC:28369): (THO complex subunit 6) This gene encodes a subunit of the multi-protein THO complex, which is involved in coordination between transcription and mRNA processing. The THO complex is a component of the TREX (transcription/export) complex, which is involved in transcription and export of mRNAs. A missense mutation in this gene is associated with a neurodevelopmental disorder called Beaulieu-Boycott-Innes syndrome. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110079765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC6	NM_024339.5	c.41C>A	p.Thr14Lys	missense_variant, splice_region_variant	Exon 2 of 13	ENST00000326266.13	NP_077315.2
THOC6	NM_001347704.2	c.41C>A	p.Thr14Lys	missense_variant, splice_region_variant	Exon 3 of 14		NP_001334633.1
THOC6	NM_001142350.3	c.41C>A	p.Thr14Lys	missense_variant, splice_region_variant	Exon 2 of 12		NP_001135822.1
THOC6	NM_001347703.2	c.-29-3C>A		splice_region_variant, intron_variant	Intron 2 of 13		NP_001334632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC6	ENST00000326266.13	c.41C>A	p.Thr14Lys	missense_variant, splice_region_variant	Exon 2 of 13	1	NM_024339.5	ENSP00000326531.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461322 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727004

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.41C>A (p.T14K) alteration is located in exon 2 (coding exon 2) of the THOC6 gene. This alteration results from a C to A substitution at nucleotide position 41, causing the threonine (T) at amino acid position 14 to be replaced by a lysine (K). 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	0.091
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.76
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.39	N;N
REVEL	Benign	0.046
Sift4G	Benign	0.79	T;T
Polyphen		0.0040	B;B
Vest4		0.32
MutPred		0.59		Loss of catalytic residue at T14 (P = 0.0146);Loss of catalytic residue at T14 (P = 0.0146);
MVP		0.68
MPC		0.11
ClinPred		0.036	T
GERP RS		1.9
Varity_R		0.063
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3075710;