22-29533250-G-A

Variant names:

• chr22-29533250-G-A
• rs8135828
• NM_003678.5:c.715-1287C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003678.5(THOC5):​c.715-1287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,234 control chromosomes in the GnomAD database, including 1,964 homozygotes. 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: 𝑓 0.14 (1964 hom., cov: 33)
• Consequence: THOC5 NM_003678.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 13 publications found

Genes affected

THOC5 (HGNC:19074): (THO complex subunit 5) Predicted to enable mRNA binding activity. Involved in several processes, including monocyte differentiation; negative regulation of DNA damage checkpoint; and viral mRNA export from host cell nucleus. Located in nucleoplasm. Part of THO complex part of transcription export complex. Colocalizes with chromosome, telomeric region. Implicated in breast carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000234208 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003678.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC5	NM_003678.5	MANE Select	c.715-1287C>T		intron	N/A	NP_003669.4
	THOC5	NM_001002877.2		c.715-1287C>T		intron	N/A	NP_001002877.1
	THOC5	NM_001002878.1		c.715-1287C>T		intron	N/A	NP_001002878.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC5	ENST00000490103.6	TSL:1 MANE Select	c.715-1287C>T		intron	N/A	ENSP00000420306.1
	THOC5	ENST00000397871.5	TSL:5	c.715-1287C>T		intron	N/A	ENSP00000380969.1
	THOC5	ENST00000397872.5	TSL:5	c.715-1287C>T		intron	N/A	ENSP00000380970.1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21419 AN: 152116 Hom.: 1969 Cov.: 33

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.141 AC: 21407 AN: 152234 Hom.: 1964 Cov.: 33 AF XY: 0.140 AC XY: 10448 AN XY: 74438

African (AFR) AF: 0.0406 AC: 1687 AN: 41556

American (AMR) AF: 0.162 AC: 2479 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 812 AN: 3470

East Asian (EAS) AF: 0.415 AC: 2143 AN: 5162

South Asian (SAS) AF: 0.133 AC: 640 AN: 4826

European-Finnish (FIN) AF: 0.138 AC: 1457 AN: 10594

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11685 AN: 68004

Other (OTH) AF: 0.155 AC: 329 AN: 2116

Alfa AF: 0.163 Hom.: 6336

Bravo AF: 0.143

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs8135828; hg19: chr22-29929239;