rs3741691

Positions:

• chr12-71664636-G-T

Variant summary

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

The ENST00000308086.3(THAP2):​c.71+56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,592,760 control chromosomes in the GnomAD database, including 49,911 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 0.29 (9543 hom., cov: 32)
  • Exomes 𝑓: 0.19 (40368 hom.)
• Consequence: THAP2 ENST00000308086.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

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]

ZFC3H1 (HGNC:28328): (zinc finger C3H1-type containing) Predicted to enable metal ion binding activity. Predicted to be involved in RNA processing. Located in nucleus. Part of exosome (RNase complex). [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
THAP2	NM_031435.4	c.71+56G>T		intron_variant		ENST00000308086.3	NP_113623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
THAP2	ENST00000308086.3	c.71+56G>T		intron_variant		1	NM_031435.4	ENSP00000310796	P1
THAP2	ENST00000547843.1	c.71+56G>T		intron_variant		2		ENSP00000449826
ZFC3H1	ENST00000550712.1	n.205+2885C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44341 AN: 151916 Hom.: 9518 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.189 AC: 272978 AN: 1440726 Hom.: 40368 Cov.: 26 AF XY: 0.194 AC XY: 139371 AN XY: 718136

Gnomad4 AFR exome AF: 0.543

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.802

Gnomad4 SAS exome AF: 0.406

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.292 AC: 44419 AN: 152034 Hom.: 9543 Cov.: 32 AF XY: 0.299 AC XY: 22203 AN XY: 74318

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.271

Alfa AF: 0.169 Hom.: 6256

Bravo AF: 0.307

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.4
DANN	Benign	0.82

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: rs3741691; hg19: chr12-72058416;