7-108564422-T-A

Variant summary

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

The NM_001130475.3(THAP5):c.957A>T(p.Gln319His) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: THAP5 NM_001130475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12

Genes affected

THAP5 (HGNC:23188): (THAP domain containing 5) Enables protease binding activity. Involved in negative regulation of cell cycle and negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PNPLA8 (HGNC:28900): (patatin like phospholipase domain containing 8) This gene encodes a member of the patatin-like phospholipase domain containing protein family. Members of this family are phospholipases which catalyze the cleavage of fatty acids from membrane phospholipids. The product of this gene is a calcium-independent phospholipase. Mutations in this gene have been associated with mitochondrial myopathy with lactic acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2015]

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=0.22544056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP5	NM_001130475.3	c.957A>T	p.Gln319His	missense_variant	3/3	ENST00000415914.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP5	ENST00000415914.4	c.957A>T	p.Gln319His	missense_variant	3/3	1	NM_001130475.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461588 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727112

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2021

The c.957A>T (p.Q319H) alteration is located in exon 3 (coding exon 3) of the THAP5 gene. This alteration results from a A to T substitution at nucleotide position 957, causing the glutamine (Q) at amino acid position 319 to be replaced by a histidine (H). 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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.092
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	0.94	N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.61
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.45
MutPred		0.38		Loss of catalytic residue at Q319 (P = 0.0076);.;
MVP		0.48
MPC		0.46
ClinPred		0.84	D
GERP RS		0.36
Varity_R		0.14
gMVP		0.37

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: chr7-108204866;