NM_003678.5:c.971G>A

Variant names:

• chr22-29528173-C-T
• rs768917796
• NM_003678.5:c.971G>A

Variant summary

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

The NM_003678.5(THOC5):​c.971G>A​(p.Arg324His) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: THOC5 NM_003678.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97
• Publications: 0 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: 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_003678.5. 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
	THOC5	NM_003678.5	MANE Select	c.971G>A	p.Arg324His	missense	Exon 11 of 20	NP_003669.4
	THOC5	NM_001002877.2		c.971G>A	p.Arg324His	missense	Exon 12 of 21	NP_001002877.1	Q13769
	THOC5	NM_001002878.1		c.971G>A	p.Arg324His	missense	Exon 12 of 21	NP_001002878.1	Q13769

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THOC5	ENST00000490103.6	TSL:1 MANE Select	c.971G>A	p.Arg324His	missense	Exon 11 of 20	ENSP00000420306.1	Q13769
	THOC5	ENST00000853420.1		c.1121G>A	p.Arg374His	missense	Exon 12 of 21	ENSP00000523479.1
	THOC5	ENST00000928658.1		c.1025G>A	p.Arg342His	missense	Exon 13 of 22	ENSP00000598717.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251366 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.62		Loss of MoRF binding (P = 0.0762)
MVP		0.53
MPC		0.83
ClinPred		0.79	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.46
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs768917796; hg19: chr22-29924162;