rs561512265

Variant names:

• chr22-21000010-C-T
• rs561512265
• NM_030573.3:c.800G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21000010-C-T
• chr22-21000010-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030573.3(THAP7):​c.800G>A​(p.Arg267Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,580 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R267W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: THAP7 NM_030573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.601
• Publications: 0 publications found

Genes affected

THAP7 (HGNC:23190): (THAP domain containing 7) Enables several functions, including C2H2 zinc finger domain binding activity; histone binding activity; and histone deacetylase binding activity. Involved in negative regulation of histone acetylation and negative regulation of transcription by RNA polymerase II. Located in nuclear membrane and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27962703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030573.3. 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
	THAP7	NM_030573.3	MANE Select	c.800G>A	p.Arg267Gln	missense	Exon 4 of 4	NP_085050.2	Q9BT49
	THAP7	NM_001008695.1		c.800G>A	p.Arg267Gln	missense	Exon 5 of 5	NP_001008695.1	Q9BT49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP7	ENST00000215742.9	TSL:1 MANE Select	c.800G>A	p.Arg267Gln	missense	Exon 4 of 4	ENSP00000215742.4	Q9BT49
	THAP7	ENST00000399133.2	TSL:2	c.800G>A	p.Arg267Gln	missense	Exon 5 of 5	ENSP00000382084.2	Q9BT49
	THAP7	ENST00000917978.1		c.644G>A	p.Arg215Gln	missense	Exon 3 of 3	ENSP00000588037.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000495 AC: 12 AN: 242492 AF XY: 0.0000377

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1460232 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726446

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.000134 AC: 6 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26106

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111882

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152348 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74500

African (AFR) AF: 0.0000241 AC: 1 AN: 41578

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

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

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000331 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	0.87
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	-0.098
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.77	D
MetaRNN	Benign	0.28	T
MetaSVM	Pathogenic	0.81	D
MutationAssessor	Benign	0.55	N
PhyloP100		0.60
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.52
Sift	Benign	0.16	T
Sift4G	Uncertain	0.021	D
Polyphen		0.31	B
Vest4		0.56
MutPred		0.20		Loss of methylation at R267 (P = 0.0413)
MVP		0.99
MPC		1.4
ClinPred		0.19	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.091
gMVP		0.74
Mutation Taster		=86/14	polymorphism

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: rs561512265; hg19: chr22-21354299;