22-21000010-C-G

Variant names:

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

Variant summary

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

The NM_030573.3(THAP7):​c.800G>C​(p.Arg267Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 33)
• Consequence: THAP7 NM_030573.3 missense
• Clinical Significance: Not reported in ClinVar
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Arg267Pro	missense	Exon 4 of 4	NP_085050.2	Q9BT49
	THAP7	NM_001008695.1		c.800G>C	p.Arg267Pro	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>C	p.Arg267Pro	missense	Exon 4 of 4	ENSP00000215742.4	Q9BT49
	THAP7	ENST00000399133.2	TSL:2	c.800G>C	p.Arg267Pro	missense	Exon 5 of 5	ENSP00000382084.2	Q9BT49
	THAP7	ENST00000917978.1		c.644G>C	p.Arg215Pro	missense	Exon 3 of 3	ENSP00000588037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Benign	0.55	N
PhyloP100		0.60
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.26		Gain of loop (P = 0)
MVP		1.0
MPC		1.5
ClinPred		0.76	D
GERP RS		4.1
Varity_R		0.63
gMVP		0.88
Mutation Taster		=68/32	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;