chr22-29511861-G-T

Variant names:

• chr22-29511861-G-T
• rs2074948
• NM_003678.5:c.1797+160C>A

Variant summary

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

The NM_003678.5(THOC5):​c.1797+160C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,156 control chromosomes in the GnomAD database, including 3,342 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 0.20 (3342 hom., cov: 33)
• Consequence: THOC5 NM_003678.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THOC5	NM_003678.5	c.1797+160C>A		intron_variant	Intron 18 of 19	ENST00000490103.6	NP_003669.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THOC5	ENST00000490103.6	c.1797+160C>A		intron_variant	Intron 18 of 19	1	NM_003678.5	ENSP00000420306.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30187 AN: 152036 Hom.: 3345 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.198 AC: 30190 AN: 152156 Hom.: 3342 Cov.: 33 AF XY: 0.196 AC XY: 14610 AN XY: 74378

African (AFR) AF: 0.118 AC: 4903 AN: 41526

American (AMR) AF: 0.210 AC: 3209 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2222 AN: 5170

South Asian (SAS) AF: 0.189 AC: 909 AN: 4820

European-Finnish (FIN) AF: 0.187 AC: 1982 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15298 AN: 67972

Other (OTH) AF: 0.223 AC: 471 AN: 2112

Alfa AF: 0.126 Hom.: 301

Bravo AF: 0.202

Asia WGS AF: 0.272 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.36
PhyloP100		-0.94
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: rs2074948; hg19: chr22-29907850;