rs6765857

Variant names:

• chr3-141331963-A-G
• rs6765857
• ENST00000509842.5:c.-739+7507A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.8).
• 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 rank	MANE	Protein	UniProt
ZBTB38	NM_001080412.3	c.-739+7507A>G		intron_variant	Intron 1 of 7		NP_001073881.2
ZBTB38	XM_047447849.1	c.-567+7507A>G		intron_variant	Intron 1 of 7		XP_047303805.1
ZBTB38	XM_047447855.1	c.-494+7507A>G		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.-739+7507A>G		intron_variant	Intron 1 of 7	1		ENSP00000426931.1
ENSG00000249417	ENST00000507698.1	n.166+34338T>C		intron_variant	Intron 2 of 2	3
PXYLP1	ENST00000637579.1	n.*289+20207A>G		intron_variant	Intron 6 of 6	5		ENSP00000490114.1

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

African (AFR) AF: 0.319 AC: 13203 AN: 41442

American (AMR) AF: 0.245 AC: 3743 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3462

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5176

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4816

European-Finnish (FIN) AF: 0.423 AC: 4464 AN: 10554

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27444 AN: 67968

Other (OTH) AF: 0.315 AC: 666 AN: 2114

Alfa AF: 0.384 Hom.: 9935

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
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs6765857; hg19: chr3-141050805;