chr16-3025974-T-G

Variant names:

• chr16-3025974-T-G
• NM_024339.5:c.206T>G

Variant summary

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

The NM_024339.5(THOC6):​c.206T>G​(p.Val69Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THOC6 NM_024339.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.52

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC6	NM_024339.5	c.206T>G	p.Val69Gly	missense_variant	Exon 3 of 13	ENST00000326266.13	NP_077315.2
THOC6	NM_001347704.2	c.206T>G	p.Val69Gly	missense_variant	Exon 4 of 14		NP_001334633.1
THOC6	NM_001347703.2	c.134T>G	p.Val45Gly	missense_variant	Exon 4 of 14		NP_001334632.1
THOC6	NM_001142350.3	c.206T>G	p.Val69Gly	missense_variant	Exon 3 of 12		NP_001135822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC6	ENST00000326266.13	c.206T>G	p.Val69Gly	missense_variant	Exon 3 of 13	1	NM_024339.5	ENSP00000326531.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.26	T;.;.;.
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.74	T;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;.;L
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	D;.;.;D
REVEL	Benign	0.18
Sift4G	Uncertain	0.027	D;D;D;D
Polyphen		0.21	B;.;.;B
Vest4		0.43
MutPred		0.57		Gain of disorder (P = 0.0174);.;.;Gain of disorder (P = 0.0174);
MVP		0.56
MPC		0.16
ClinPred		0.69	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: -13

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: chr16-3075975;