22-21000280-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP7	NM_030573.3	c.530A>T	p.Asp177Val	missense_variant	Exon 4 of 4	ENST00000215742.9	NP_085050.2
THAP7	NM_001008695.1	c.530A>T	p.Asp177Val	missense_variant	Exon 5 of 5		NP_001008695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP7	ENST00000215742.9	c.530A>T	p.Asp177Val	missense_variant	Exon 4 of 4	1	NM_030573.3	ENSP00000215742.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530A>T (p.D177V) alteration is located in exon 4 (coding exon 4) of the THAP7 gene. This alteration results from a A to T substitution at nucleotide position 530, causing the aspartic acid (D) at amino acid position 177 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Benign	0.34	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.44
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.014	D;D
Polyphen		0.98	D;D
Vest4		0.75
MutPred		0.20		Loss of phosphorylation at S176 (P = 0.137);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-21354569;