ENST00000509842.5:c.-738-12501G>A

Variant names:

• chr3-141356120-G-A
• rs13095453
• ENST00000509842.5:c.-738-12501G>A

Variant summary

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

The ENST00000509842.5(ZBTB38):​c.-738-12501G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,932 control chromosomes in the GnomAD database, including 5,902 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 0.26 (5902 hom., cov: 32)
• Consequence: ZBTB38 ENST00000509842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 9 publications found

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]

ENSG00000249417 (HGNC:):

PXYLP1 (HGNC:26303): (2-phosphoxylose phosphatase 1) Enables phosphatase activity. Involved in chondroitin sulfate proteoglycan biosynthetic process; glycosaminoglycan biosynthetic process; and positive regulation of heparan sulfate proteoglycan biosynthetic process. Located in Golgi apparatus. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB38	NM_001080412.3	c.-738-12501G>A		intron_variant	Intron 1 of 7		NP_001073881.2
ZBTB38	XM_047447849.1	c.-566-12501G>A		intron_variant	Intron 1 of 7		XP_047303805.1
ZBTB38	XM_047447855.1	c.-493-12501G>A		intron_variant	Intron 1 of 6		XP_047303811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000509842.5	c.-738-12501G>A		intron_variant	Intron 1 of 7	1		ENSP00000426931.1
ENSG00000249417	ENST00000507698.1	n.166+10181C>T		intron_variant	Intron 2 of 2	3
PXYLP1	ENST00000637579.1	n.*290-10126G>A		intron_variant	Intron 6 of 6	5		ENSP00000490114.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40101 AN: 151814 Hom.: 5903 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 40106 AN: 151932 Hom.: 5902 Cov.: 32 AF XY: 0.260 AC XY: 19336 AN XY: 74258

African (AFR) AF: 0.216 AC: 8933 AN: 41384

American (AMR) AF: 0.178 AC: 2721 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3468

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5174

South Asian (SAS) AF: 0.177 AC: 851 AN: 4816

European-Finnish (FIN) AF: 0.385 AC: 4067 AN: 10558

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21682 AN: 67952

Other (OTH) AF: 0.227 AC: 478 AN: 2104

Alfa AF: 0.289 Hom.: 18717

Bravo AF: 0.246

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.61
PhyloP100		0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13095453; hg19: chr3-141074962;