Genetic Variant ZBTB10:c.972+128G>C (chr8-80487910-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001105539.3(ZBTB10):c.972+128G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,115,586 control chromosomes in the GnomAD database, including 861 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.027 ( 79 hom., cov: 32)

Exomes 𝑓: 0.038 ( 782 hom. )

Consequence

ZBTB10
NM_001105539.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.239

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
ZBTB10	NM_001105539.3	MANE Select	c.972+128G>C	intron	N/A	NP_001099009.1	Q96DT7-1
ZBTB10	NM_023929.5		c.972+128G>C	intron	N/A	NP_076418.3
ZBTB10	NM_001277145.2		c.96+2031G>C	intron	N/A	NP_001264074.1	Q96DT7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZBTB10	ENST00000455036.8	TSL:2 MANE Select	c.972+128G>C	intron	N/A	ENSP00000412036.3	Q96DT7-1
ZBTB10	ENST00000430430.5	TSL:5	c.972+128G>C	intron	N/A	ENSP00000387462.1	Q96DT7-1
ZBTB10	ENST00000961791.1		c.972+128G>C	intron	N/A	ENSP00000631850.1

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4183

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0430

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0507

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0380

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.0376

AC:

36179

AN:

963346

Hom.:

782

AF XY:

0.0382

AC XY:

18183

AN XY:

475626

show subpopulations

African (AFR)

AF:

0.0118

AC:

258

AN:

21834

American (AMR)

AF:

0.0203

AC:

372

AN:

18326

Ashkenazi Jewish (ASJ)

AF:

0.0381

AC:

639

AN:

16764

East Asian (EAS)

AF:

0.0000911

AC:

AN:

32946

South Asian (SAS)

AF:

0.0561

AC:

2854

AN:

50902

European-Finnish (FIN)

AF:

0.0354

AC:

1055

AN:

29796

Middle Eastern (MID)

AF:

0.0538

AC:

164

AN:

3050

European-Non Finnish (NFE)

AF:

0.0392

AC:

29277

AN:

746838

Other (OTH)

AF:

0.0363

AC:

1557

AN:

42890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1657

3314

4971

6628

8285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1040

2080

3120

4160

5200

<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:

0.0275

AC:

4183

AN:

152240

Hom.:

Cov.:

AF XY:

0.0262

AC XY:

1947

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0105

AC:

437

AN:

41540

American (AMR)

AF:

0.0199

AC:

305

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0430

AC:

149

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0512

AC:

247

AN:

4828

European-Finnish (FIN)

AF:

0.0328

AC:

348

AN:

10596

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0380

AC:

2583

AN:

68002

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

205

411

616

822

1027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0148

Hom.:

Bravo

AF:

0.0250

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.9

(source)

DANN

Benign

0.58

PhyloP100

-0.24

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over