chr12-71677265-A-G

Variant names:

• chr12-71677265-A-G
• rs10748180
• NM_031435.4:c.*157A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ENSG00000258064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
THAP2	NM_031435.4	c.*157A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000308086.3	NP_113623.1
LOC124902965	XR_007063367.1	n.144-5483T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
THAP2	ENST00000308086.3	c.*157A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_031435.4	ENSP00000310796.2
ENSG00000258064	ENST00000548802.1	n.195+2867A>G		intron_variant	Intron 1 of 4	3		ENSP00000454911.2
ENSG00000306515	ENST00000819198.1	n.154-5483T>C		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.813 AC: 9293 AN: 11428

American (AMR) AF: 0.455 AC: 4458 AN: 9788

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 2707 AN: 10944

East Asian (EAS) AF: 0.818 AC: 19912 AN: 24352

South Asian (SAS) AF: 0.569 AC: 7272 AN: 12778

European-Finnish (FIN) AF: 0.346 AC: 7438 AN: 21514

Middle Eastern (MID) AF: 0.331 AC: 587 AN: 1776

European-Non Finnish (NFE) AF: 0.271 AC: 105496 AN: 389094

Other (OTH) AF: 0.366 AC: 9126 AN: 24940

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

African (AFR) AF: 0.810 AC: 33628 AN: 41508

American (AMR) AF: 0.429 AC: 6556 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 896 AN: 3468

East Asian (EAS) AF: 0.827 AC: 4289 AN: 5186

South Asian (SAS) AF: 0.596 AC: 2872 AN: 4816

European-Finnish (FIN) AF: 0.352 AC: 3719 AN: 10574

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18624 AN: 67952

Other (OTH) AF: 0.435 AC: 918 AN: 2112

Alfa AF: 0.342 Hom.: 23604

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs10748180; hg19: chr12-72071045;