22-21000260-C-T

Variant names:

• chr22-21000260-C-T
• NM_030573.3:c.550G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030573.3(THAP7):​c.550G>A​(p.Ala184Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,405,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: THAP7 NM_030573.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.196

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16492975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
THAP7	NM_030573.3	c.550G>A	p.Ala184Thr	missense_variant	Exon 4 of 4	ENST00000215742.9	NP_085050.2
THAP7	NM_001008695.1	c.550G>A	p.Ala184Thr	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.550G>A	p.Ala184Thr	missense_variant	Exon 4 of 4	1	NM_030573.3	ENSP00000215742.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1405074 Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 2 AN XY: 693712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.550G>A (p.A184T) alteration is located in exon 4 (coding exon 4) of the THAP7 gene. This alteration results from a G to A substitution at nucleotide position 550, causing the alanine (A) at amino acid position 184 to be replaced by a threonine (T). 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	0.072
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.078
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.71	.;T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.20	N;N
REVEL	Benign	0.27
Sift	Benign	0.34	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.34	B;B
Vest4		0.29
MutPred		0.12		Gain of phosphorylation at A184 (P = 0.0131);Gain of phosphorylation at A184 (P = 0.0131);
MVP		0.93
MPC		0.45
ClinPred		0.23	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr22-21354549;