16-3026097-C-A

Variant names:

• chr16-3026097-C-A
• rs765460462
• NM_024339.5:c.255C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024339.5(THOC6):​c.255C>A​(p.Thr85Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. T85T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: THOC6 NM_024339.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.63
• Publications: 1 publications found

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]

THOC6 Gene-Disease associations (from GenCC):

• THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024339.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC6	NM_024339.5	MANE Select	c.255C>A	p.Thr85Thr	synonymous	Exon 4 of 13	NP_077315.2
	THOC6	NM_001347704.2		c.255C>A	p.Thr85Thr	synonymous	Exon 5 of 14	NP_001334633.1	Q86W42-1
	THOC6	NM_001347703.2		c.183C>A	p.Thr61Thr	synonymous	Exon 5 of 14	NP_001334632.1	Q86W42-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC6	ENST00000326266.13	TSL:1 MANE Select	c.255C>A	p.Thr85Thr	synonymous	Exon 4 of 13	ENSP00000326531.8	Q86W42-1
	THOC6	ENST00000574549.5	TSL:1	c.183C>A	p.Thr61Thr	synonymous	Exon 5 of 14	ENSP00000458295.1	Q86W42-2
	THOC6	ENST00000571057.5	TSL:1	n.713C>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		-7.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.46		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.46		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765460462; hg19: chr16-3076098;