12-71677265-A-G

Position:

• chr12-71677265-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031435.4(THAP2):​c.*157A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 658,704 control chromosomes in the GnomAD database, including 55,220 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (21405 hom., cov: 33)
  • Exomes 𝑓: 0.33 (33815 hom.)
• Consequence: THAP2 NM_031435.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

THAP2 (HGNC:20854): (THAP domain containing 2) Predicted to enable DNA binding activity and metal ion binding activity. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902965 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
THAP2	NM_031435.4	c.*157A>G		3_prime_UTR_variant	3/3	ENST00000308086.3
LOC124902965	XR_007063367.1	n.144-5483T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
THAP2	ENST00000308086.3	c.*157A>G		3_prime_UTR_variant	3/3	1	NM_031435.4	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71728 AN: 151972 Hom.: 21357 Cov.: 33

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.328 AC: 166289 AN: 506614 Hom.: 33815 Cov.: 7 AF XY: 0.328 AC XY: 82147 AN XY: 250594

Gnomad4 AFR exome AF: 0.813

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.818

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.472 AC: 71829 AN: 152090 Hom.: 21405 Cov.: 33 AF XY: 0.480 AC XY: 35680 AN XY: 74352

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.435

Alfa AF: 0.295 Hom.: 8706

Bravo AF: 0.494

Asia WGS AF: 0.667 AC: 2308 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.26

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

LitVar

Other links and lift over

dbSNP: rs10748180; hg19: chr12-72071045;