Genetic Variant NM_001105539.3:c.140C>A (chr8-80486950-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105539.3(ZBTB10):c.140C>A(p.Pro47His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,362,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P47S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

ZBTB10
NM_001105539.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.455

Publications

3 publications found

Variant links:

Genes affected

ZBTB10 (HGNC:30953): (zinc finger and BTB domain containing 10) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19245043).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105539.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB10	NM_001105539.3	MANE Select	c.140C>A	p.Pro47His	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
ZBTB10	NM_023929.5		c.140C>A	p.Pro47His	missense	Exon 1 of 7	NP_076418.3
ZBTB10	NM_001277145.2		c.96+1071C>A		intron	N/A	NP_001264074.1	Q96DT7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB10	ENST00000455036.8	TSL:2 MANE Select	c.140C>A	p.Pro47His	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
ZBTB10	ENST00000430430.5	TSL:5	c.140C>A	p.Pro47His	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
ZBTB10	ENST00000961791.1		c.140C>A	p.Pro47His	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000661

AC:

AN:

1362274

Hom.:

Cov.:

AF XY:

0.00000893

AC XY:

AN XY:

671872

show subpopulations

African (AFR)

AF:

0.0000359

AC:

AN:

27836

American (AMR)

AF:

0.00

AC:

AN:

32926

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24002

East Asian (EAS)

AF:

0.00

AC:

AN:

32258

South Asian (SAS)

AF:

0.00

AC:

AN:

76774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4482

European-Non Finnish (NFE)

AF:

0.00000749

AC:

AN:

1067970

Other (OTH)

AF:

0.00

AC:

AN:

56628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0044

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

0.46

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.42

REVEL

Benign

0.038

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.017

Polyphen

0.78

Vest4

0.31

MutPred

0.20

Loss of glycosylation at P47 (P = 0.005)

MVP

0.043

MPC

0.85

ClinPred

0.28

GERP RS

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.15

Mutation Taster

=95/5

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over