Genetic Variant ZBTB38:c.1-10241G>T (chr3-141432148-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001350099.2(ZBTB38):c.-190-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000338 in 985,344 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 3 hom. )

Consequence

ZBTB38
NM_001350099.2 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.926

Publications

20 publications found

Variant links:

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]

ZBTB38 links:

ENSG00000309977 (HGNC:):

ENSG00000309977 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350099.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZBTB38	NM_001376113.1	MANE Select	c.1-10241G>T	intron	N/A	NP_001363042.1	Q8NAP3
ZBTB38	NM_001080412.3		c.1-10241G>T	intron	N/A	NP_001073881.2	Q8NAP3
ZBTB38	NM_001350099.2		c.-190-4G>T	splice_region intron	N/A	NP_001337028.1	Q8NAP3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZBTB38	ENST00000321464.7	TSL:6 MANE Select	c.1-10241G>T	intron	N/A	ENSP00000372635.5	Q8NAP3
ZBTB38	ENST00000509883.5	TSL:1	c.1-10241G>T	intron	N/A	ENSP00000424254.1	D6RBC4
ZBTB38	ENST00000509842.5	TSL:1	c.1-10241G>T	intron	N/A	ENSP00000426931.1	D6RE69

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000120

AC:

100

AN:

833124

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

384724

show subpopulations

African (AFR)

AF:

0.00538

AC:

AN:

15786

American (AMR)

AF:

0.00

AC:

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5152

East Asian (EAS)

AF:

0.00

AC:

AN:

3632

South Asian (SAS)

AF:

0.00

AC:

AN:

16462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00000131

AC:

AN:

761910

Other (OTH)

AF:

0.000513

AC:

AN:

27302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00153

AC:

233

AN:

152220

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

115

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00517

AC:

215

AN:

41548

American (AMR)

AF:

0.000785

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

4763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.74

(source)

DANN

Benign

0.79

PhyloP100

-0.93

PromoterAI

-0.11

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over