rs8135828

Positions:

• chr22-29533250-G-A
• chr22-29533250-G-C
• chr22-29533250-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000490103.6(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 ENST00000490103.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THOC5	NM_003678.5	c.715-1287C>T		intron_variant		ENST00000490103.6	NP_003669.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THOC5	ENST00000490103.6	c.715-1287C>T		intron_variant		1	NM_003678.5	ENSP00000420306	P1
	ENST00000411969.1	n.161+1980C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.155

Alfa AF: 0.172 Hom.: 3747

Bravo AF: 0.143

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs8135828; hg19: chr22-29929239;