12-71664636-G-T

Variant names:

• chr12-71664636-G-T
• rs3741691
• NM_031435.4:c.71+56G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031435.4(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 NM_031435.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 11 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]

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031435.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP2	NM_031435.4	MANE Select	c.71+56G>T		intron	N/A	NP_113623.1	Q9H0W7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THAP2	ENST00000308086.3	TSL:1 MANE Select	c.71+56G>T		intron	N/A	ENSP00000310796.2	Q9H0W7
	THAP2	ENST00000547843.1	TSL:2	c.71+56G>T		intron	N/A	ENSP00000449826.1	F8VW94
	ZFC3H1	ENST00000550712.1	TSL:4	n.205+2885C>A		intron	N/A

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

African (AFR) AF: 0.543 AC: 17960 AN: 33068

American (AMR) AF: 0.287 AC: 12776 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4123 AN: 25992

East Asian (EAS) AF: 0.802 AC: 31768 AN: 39600

South Asian (SAS) AF: 0.406 AC: 34828 AN: 85782

European-Finnish (FIN) AF: 0.202 AC: 10775 AN: 53346

Middle Eastern (MID) AF: 0.216 AC: 1233 AN: 5718

European-Non Finnish (NFE) AF: 0.134 AC: 146165 AN: 1092978

Other (OTH) AF: 0.224 AC: 13350 AN: 59680

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

African (AFR) AF: 0.532 AC: 22060 AN: 41454

American (AMR) AF: 0.229 AC: 3506 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3472

East Asian (EAS) AF: 0.818 AC: 4217 AN: 5158

South Asian (SAS) AF: 0.429 AC: 2065 AN: 4816

European-Finnish (FIN) AF: 0.215 AC: 2269 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8936 AN: 67970

Other (OTH) AF: 0.271 AC: 571 AN: 2106

Alfa AF: 0.188 Hom.: 17431

Bravo AF: 0.307

Asia WGS AF: 0.551 AC: 1912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.4
DANN	Benign	0.82
PhyloP100		0.27
PromoterAI		-0.093	Neutral
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: rs3741691; hg19: chr12-72058416;