rs763344375

Variant names:

• chr16-3026101-C-G
• NM_024339.5:c.259C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-3026101-C-G
• chr16-3026101-C-T

Variant summary

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

The NM_024339.5(THOC6):​c.259C>G​(p.Arg87Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: THOC6 NM_024339.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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=0.13064769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC6	NM_024339.5	c.259C>G	p.Arg87Gly	missense_variant	Exon 4 of 13	ENST00000326266.13	NP_077315.2
THOC6	NM_001347704.2	c.259C>G	p.Arg87Gly	missense_variant	Exon 5 of 14		NP_001334633.1
THOC6	NM_001347703.2	c.187C>G	p.Arg63Gly	missense_variant	Exon 5 of 14		NP_001334632.1
THOC6	NM_001142350.3	c.259C>G	p.Arg87Gly	missense_variant	Exon 4 of 12		NP_001135822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC6	ENST00000326266.13	c.259C>G	p.Arg87Gly	missense_variant	Exon 4 of 13	1	NM_024339.5	ENSP00000326531.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456632 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 723686

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.077	T;.;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.88	D;.;D;D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N;.;.;N
REVEL	Benign	0.086
Sift4G	Benign	0.31	T;T;T;T
Polyphen		0.76	P;.;.;P
Vest4		0.32
MutPred		0.54		Gain of glycosylation at S84 (P = 0.047);.;.;Gain of glycosylation at S84 (P = 0.047);
MVP		0.33
MPC		0.14
ClinPred		0.31	T
GERP RS		3.5
Varity_R		0.72
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3076102;