chr22-21000280-T-A

Variant names:

• chr22-21000280-T-A
• NM_030573.3:c.530A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_030573.3(THAP7):​c.530A>T​(p.Asp177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: THAP7 NM_030573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.896
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

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.530A>T	p.Asp177Val	missense	Exon 4 of 4	NP_085050.2	Q9BT49
	THAP7	NM_001008695.1		c.530A>T	p.Asp177Val	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.530A>T	p.Asp177Val	missense	Exon 4 of 4	ENSP00000215742.4	Q9BT49
	THAP7	ENST00000399133.2	TSL:2	c.530A>T	p.Asp177Val	missense	Exon 5 of 5	ENSP00000382084.2	Q9BT49
	THAP7	ENST00000917978.1		c.374A>T	p.Asp125Val	missense	Exon 3 of 3	ENSP00000588037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.27
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.77	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.34	N
PhyloP100		0.90
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.44
Sift	Benign	0.13	T
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.75
MutPred		0.20		Loss of phosphorylation at S176 (P = 0.137)
MVP		0.97
MPC		1.3
ClinPred		0.87	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.60
Mutation Taster		=83/17	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

hg19: chr22-21354569;