3-141328230-C-A

Variant names:

• chr3-141328230-C-A
• rs6795197
• ENST00000509842.5:c.-739+3774C>A

Variant summary

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

The ENST00000509842.5(ZBTB38):​c.-739+3774C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,994 control chromosomes in the GnomAD database, including 8,884 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 0.33 (8884 hom., cov: 32)
• Consequence: ZBTB38 ENST00000509842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.945
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB38	NM_001080412.3	c.-739+3774C>A		intron_variant	Intron 1 of 7		NP_001073881.2
ZBTB38	XM_047447849.1	c.-567+3774C>A		intron_variant	Intron 1 of 7		XP_047303805.1
ZBTB38	XM_047447855.1	c.-494+3774C>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.-739+3774C>A		intron_variant	Intron 1 of 7	1		ENSP00000426931.1
ENSG00000249417	ENST00000507698.1	n.166+38071G>T		intron_variant	Intron 2 of 2	3
PXYLP1	ENST00000637579.1	n.*289+16474C>A		intron_variant	Intron 6 of 6	5		ENSP00000490114.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49908 AN: 151876 Hom.: 8882 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.00635

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.328 AC: 49925 AN: 151994 Hom.: 8884 Cov.: 32 AF XY: 0.323 AC XY: 23980 AN XY: 74290

African (AFR) AF: 0.286 AC: 11833 AN: 41436

American (AMR) AF: 0.230 AC: 3520 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3466

East Asian (EAS) AF: 0.00637 AC: 33 AN: 5184

South Asian (SAS) AF: 0.237 AC: 1142 AN: 4814

European-Finnish (FIN) AF: 0.404 AC: 4258 AN: 10538

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26822 AN: 67948

Other (OTH) AF: 0.300 AC: 635 AN: 2114

Alfa AF: 0.325 Hom.: 5480

Bravo AF: 0.315

Asia WGS AF: 0.127 AC: 442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.94
DANN	Benign	0.82
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs6795197; hg19: chr3-141047072;