Genetic Variant ZBTB44:p.Glu348Gly (chr11-130239872-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001301098.2(ZBTB44):c.1043A>G(p.Glu348Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZBTB44
NM_001301098.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.20

Publications

0 publications found

Variant links:

Genes affected

ZBTB44 (HGNC:25001): (zinc finger and BTB domain containing 44) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB44 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301098.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB44	NM_001301098.2	MANE Select	c.1043A>G	p.Glu348Gly	missense	Exon 3 of 8	NP_001288027.1
ZBTB44	NM_001370219.1		c.1043A>G	p.Glu348Gly	missense	Exon 3 of 6	NP_001357148.1	H0YEM9
ZBTB44	NM_001370220.1		c.1043A>G	p.Glu348Gly	missense	Exon 3 of 6	NP_001357149.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB44	ENST00000357899.9	TSL:1 MANE Select	c.1043A>G	p.Glu348Gly	missense	Exon 3 of 8	ENSP00000350574.4
ZBTB44	ENST00000530205.5	TSL:1	c.1043A>G	p.Glu348Gly	missense	Exon 2 of 6	ENSP00000434177.1	Q8NCP5-2
ZBTB44	ENST00000525842.5	TSL:1	c.1043A>G	p.Glu348Gly	missense	Exon 3 of 6	ENSP00000433457.1	Q8NCP5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

246880

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1459526

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725746

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

85656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110716

Other (OTH)

AF:

0.00

AC:

AN:

60308

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

0.10

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.97

PhyloP100

7.2

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.31

Sift

Uncertain

0.0070

Sift4G

Benign

0.24

Polyphen

0.73

Vest4

0.79

MutPred

0.28

Loss of solvent accessibility (P = 0.0017)

MVP

0.29

MPC

0.92

ClinPred

0.86

GERP RS

5.5

gMVP

0.48

Mutation Taster

=41/59

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over