rs6765857

Positions:

• chr3-141331963-A-G

Variant summary

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

The ENST00000509842.5(ZBTB38):​c.-739+7507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,020 control chromosomes in the GnomAD database, including 9,714 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 0.35 (9714 hom., cov: 32)
• Consequence: ZBTB38 ENST00000509842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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]

(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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB38	NM_001080412.3	c.-739+7507A>G		intron_variant			NP_001073881.2
ZBTB38	XM_047447849.1	c.-567+7507A>G		intron_variant			XP_047303805.1
ZBTB38	XM_047447855.1	c.-494+7507A>G		intron_variant			XP_047303811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB38	ENST00000509842.5	c.-739+7507A>G		intron_variant		1		ENSP00000426931
	ENST00000507698.1	n.166+34338T>C		intron_variant, non_coding_transcript_variant		3
PXYLP1	ENST00000637579.1	c.*289+20207A>G		intron_variant, NMD_transcript_variant		5		ENSP00000490114

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52439 AN: 151902 Hom.: 9711 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.345 AC: 52465 AN: 152020 Hom.: 9714 Cov.: 32 AF XY: 0.339 AC XY: 25172 AN XY: 74292

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.315

Alfa AF: 0.380 Hom.: 6852

Bravo AF: 0.332

Asia WGS AF: 0.138 AC: 481 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6765857; hg19: chr3-141050805;