3-141396377-T-C

Position:

• chr3-141396377-T-C

Variant summary

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

The NM_001080412.3(ZBTB38):​c.-232T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 154,892 control chromosomes in the GnomAD database, including 24,177 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 0.53 (23927 hom., cov: 32)
  • Exomes 𝑓: 0.41 (250 hom.)
• Consequence: ZBTB38 NM_001080412.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70

Genes affected

ZBTB38 (HGNC:26636): (zinc finger and BTB domain containing 38) The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001376113.1	c.-105-7550T>C		intron_variant		ENST00000321464.7	NP_001363042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000321464.7	c.-105-7550T>C		intron_variant		6	NM_001376113.1	ENSP00000372635.5

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80166 AN: 151994 Hom.: 23877 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.405 AC: 1127 AN: 2780 Hom.: 250 Cov.: 0 AF XY: 0.388 AC XY: 720 AN XY: 1858

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.443

Gnomad4 ASJ exome AF: 0.429

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.284

Gnomad4 FIN exome AF: 0.466

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.528 AC: 80282 AN: 152112 Hom.: 23927 Cov.: 32 AF XY: 0.519 AC XY: 38609 AN XY: 74360

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.449

Alfa AF: 0.476 Hom.: 2239

Bravo AF: 0.537

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.15
DANN	Benign	0.31

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: rs1582874; hg19: chr3-141115219;