Genetic Variant ZBTB38:p.Ser319Pro (chr3-141443343-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001376113.1(ZBTB38):c.955T>C(p.Ser319Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZBTB38
NM_001376113.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.609

Publications

0 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:

ENSG00000288585 (HGNC:):

ENSG00000288585 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05264768).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376113.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB38	NM_001376113.1	MANE Select	c.955T>C	p.Ser319Pro	missense	Exon 6 of 6	NP_001363042.1	Q8NAP3
ZBTB38	NM_001080412.3		c.955T>C	p.Ser319Pro	missense	Exon 8 of 8	NP_001073881.2	Q8NAP3
ZBTB38	NM_001350099.2		c.955T>C	p.Ser319Pro	missense	Exon 6 of 6	NP_001337028.1	Q8NAP3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB38	ENST00000321464.7	TSL:6 MANE Select	c.955T>C	p.Ser319Pro	missense	Exon 6 of 6	ENSP00000372635.5	Q8NAP3
ZBTB38	ENST00000509883.5	TSL:1	c.955T>C	p.Ser319Pro	missense	Exon 3 of 3	ENSP00000424254.1	D6RBC4
ZBTB38	ENST00000441582.2	TSL:2	c.955T>C	p.Ser319Pro	missense	Exon 2 of 2	ENSP00000406955.2	Q8NAP3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.96

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0070

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.46

M_CAP

Benign

0.0054

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.23

PhyloP100

-0.61

PrimateAI

Benign

0.27

PROVEAN

Benign

0.42

REVEL

Benign

0.021

Sift

Benign

0.35

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.054

MutPred

0.23

Loss of phosphorylation at S319 (P = 0.0197)

MVP

0.068

MPC

0.52

ClinPred

0.059

GERP RS

-2.6

Varity_R

0.045

gMVP

0.14

Mutation Taster

=92/8

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over