12-71677265-A-C

Position:

• chr12-71677265-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031435.4(THAP2):​c.*157A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 660,184 control chromosomes in the GnomAD database, including 1 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 0.00083 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (1 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000835 AC: 127 AN: 152042 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000717 AC: 364 AN: 508024 Hom.: 1 Cov.: 7 AF XY: 0.000796 AC XY: 200 AN XY: 251234

Gnomad4 AFR exome AF: 0.0000874

Gnomad4 AMR exome AF: 0.000918

Gnomad4 ASJ exome AF: 0.0178

Gnomad4 EAS exome AF: 0.0000410

Gnomad4 SAS exome AF: 0.0000780

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000236

Gnomad4 OTH exome AF: 0.00228

GnomAD4 genome AF: 0.000835 AC: 127 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.000780 AC XY: 58 AN XY: 74390

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000530

Gnomad4 OTH AF: 0.00189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.084
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;