Genetic Variant NM_152735.4:c.338A>C (chr6-33455438-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152735.4(ZBTB9):c.338A>C(p.Asp113Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D113V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZBTB9
NM_152735.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.47

Publications

0 publications found

Variant links:

Genes affected

ZBTB9 (HGNC:28323): (zinc finger and BTB domain containing 9) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2831626).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152735.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB9	NM_152735.4	MANE Select	c.338A>C	p.Asp113Ala	missense	Exon 2 of 2	NP_689948.1	Q96C00

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB9	ENST00000395064.3	TSL:1 MANE Select	c.338A>C	p.Asp113Ala	missense	Exon 2 of 2	ENSP00000378503.2	Q96C00
ZBTB9	ENST00000932373.1		c.338A>C	p.Asp113Ala	missense	Exon 2 of 2	ENSP00000602432.1
ZBTB9	ENST00000932374.1		c.338A>C	p.Asp113Ala	missense	Exon 2 of 2	ENSP00000602433.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251174

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111934

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Benign

0.10

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.57

M_CAP

Benign

0.019

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PhyloP100

4.5

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.26

REVEL

Benign

0.20

Sift

Benign

0.26

Sift4G

Benign

0.39

Polyphen

0.82

Vest4

0.34

MutPred

0.49

Gain of methylation at R109 (P = 0.0726)

MVP

0.82

MPC

0.64

ClinPred

0.77

GERP RS

5.0

PromoterAI

0.017

Neutral

(source)

Varity_R

0.22

gMVP

0.73

Mutation Taster

=39/61

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over