rs9857275

Variant names:

• chr3-141359346-C-A
• rs9857275
• ENST00000509842.5:c.-738-9275C>A

Variant summary

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

The ENST00000509842.5(ZBTB38):​c.-738-9275C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,120 control chromosomes in the GnomAD database, including 5,972 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 0.27 (5972 hom., cov: 32)
• Consequence: ZBTB38 ENST00000509842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB38	NM_001080412.3	c.-738-9275C>A		intron_variant	Intron 1 of 7		NP_001073881.2
ZBTB38	XM_047447849.1	c.-566-9275C>A		intron_variant	Intron 1 of 7		XP_047303805.1
ZBTB38	XM_047447855.1	c.-493-9275C>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.-738-9275C>A		intron_variant	Intron 1 of 7	1		ENSP00000426931.1
ENSG00000249417	ENST00000507698.1	n.166+6955G>T		intron_variant	Intron 2 of 2	3
PXYLP1	ENST00000637579.1	n.*290-6900C>A		intron_variant	Intron 6 of 6	5		ENSP00000490114.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40734 AN: 152002 Hom.: 5973 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.268 AC: 40737 AN: 152120 Hom.: 5972 Cov.: 32 AF XY: 0.264 AC XY: 19636 AN XY: 74354

African (AFR) AF: 0.239 AC: 9931 AN: 41474

American (AMR) AF: 0.173 AC: 2654 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.177 AC: 855 AN: 4828

European-Finnish (FIN) AF: 0.385 AC: 4073 AN: 10568

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21370 AN: 67982

Other (OTH) AF: 0.227 AC: 479 AN: 2112

Alfa AF: 0.293 Hom.: 13863

Bravo AF: 0.251

Asia WGS AF: 0.0880 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs9857275; hg19: chr3-141078188;