NM_024339.5:c.93C>T

Variant names:

• chr16-3025761-C-T
• rs115250573
• NM_024339.5:c.93C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_024339.5(THOC6):​c.93C>T​(p.Ser31Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,614,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: THOC6 NM_024339.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.104
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 16-3025761-C-T is Benign according to our data. Variant chr16-3025761-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 718042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.104 with no splicing effect.

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.93C>T	p.Ser31Ser	synonymous	Exon 2 of 13	NP_077315.2
	THOC6	NM_001347704.2		c.93C>T	p.Ser31Ser	synonymous	Exon 3 of 14	NP_001334633.1	Q86W42-1
	THOC6	NM_001347703.2		c.21C>T	p.Ser7Ser	synonymous	Exon 3 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.93C>T	p.Ser31Ser	synonymous	Exon 2 of 13	ENSP00000326531.8	Q86W42-1
	THOC6	ENST00000574549.5	TSL:1	c.21C>T	p.Ser7Ser	synonymous	Exon 3 of 14	ENSP00000458295.1	Q86W42-2
	THOC6	ENST00000571057.5	TSL:1	n.377C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000286 AC: 72 AN: 251480 AF XY: 0.000302

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000404

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000332 AC: 485 AN: 1461888 Hom.: 0 Cov.: 36 AF XY: 0.000318 AC XY: 231 AN XY: 727244

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.000402 AC: 18 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000385 AC: 428 AN: 1112012

Other (OTH) AF: 0.000215 AC: 13 AN: 60396

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74510

African (AFR) AF: 0.000144 AC: 6 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000290 Hom.: 0

Bravo AF: 0.000261

EpiCase AF: 0.000382

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	0.45
DANN	Benign	0.90
PhyloP100		-0.10

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

Other links and lift over

dbSNP: rs115250573; hg19: chr16-3075762;