22-21000085-C-A

Variant names:

• chr22-21000085-C-A
• rs759973415
• NM_030573.3:c.725G>T

Variant summary

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

The NM_030573.3(THAP7):​c.725G>T​(p.Arg242Leu) 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. R242Q) 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: 1.80
• 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.725G>T	p.Arg242Leu	missense	Exon 4 of 4	NP_085050.2	Q9BT49
	THAP7	NM_001008695.1		c.725G>T	p.Arg242Leu	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.725G>T	p.Arg242Leu	missense	Exon 4 of 4	ENSP00000215742.4	Q9BT49
	THAP7	ENST00000399133.2	TSL:2	c.725G>T	p.Arg242Leu	missense	Exon 5 of 5	ENSP00000382084.2	Q9BT49
	THAP7	ENST00000917978.1		c.569G>T	p.Arg190Leu	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	0.83
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.69	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Benign	0.55	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.64
MutPred		0.39		Loss of MoRF binding (P = 0.014)
MVP		0.98
MPC		1.4
ClinPred		0.78	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.18
gMVP		0.64
Mutation Taster		=75/25	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: rs759973415; hg19: chr22-21354374;