rs765085960

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181842.3(ZBTB12):c.520C>T(p.Pro174Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000251 in 1,592,832 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ZBTB12
NM_181842.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Publications

0 publications found

Variant links:

Genes affected

ZBTB12 (HGNC:19066): (zinc finger and BTB domain containing 12) Enables sequence-specific double-stranded 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]

ZBTB12 links:

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

C2 Gene-Disease associations (from GenCC):

complement component 2 deficiency
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061162412).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB12	NM_181842.3	MANE Select	c.520C>T	p.Pro174Ser	missense	Exon 2 of 2	NP_862825.1	Q9Y330
C2	NM_001282457.2		c.-64+2844G>A		intron	N/A	NP_001269386.1	B4DQI1
C2	NM_001178063.3		c.-281G>A		upstream_gene	N/A	NP_001171534.1	P06681-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZBTB12	ENST00000375527.3	TSL:1 MANE Select	c.520C>T	p.Pro174Ser	missense	Exon 2 of 2	ENSP00000364677.2	Q9Y330
C2	ENST00000695637.1		c.-360+2511G>A		intron	N/A	ENSP00000512074.1	A0A8Q3WKN5
C2	ENST00000497706.6	TSL:5	c.-64+2844G>A		intron	N/A	ENSP00000417482.2	E9PDZ0

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000817

AC:

AN:

232612

AF XY:

0.000103

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:

0.000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000267

AC:

384

AN:

1440696

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

195

AN XY:

713720

show subpopulations

African (AFR)

AF:

0.0000906

AC:

AN:

33128

American (AMR)

AF:

0.0000458

AC:

AN:

43694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24706

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.000338

AC:

372

AN:

1099808

Other (OTH)

AF:

0.000101

AC:

AN:

59474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000105

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000909

AC:

ClinVar

ClinVar submissions as Germline

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

Benign

-0.41

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.032

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

PhyloP100

4.5

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.91

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.26

MVP

0.068

MPC

2.0

ClinPred

0.12

GERP RS

3.4

PromoterAI

0.039

Neutral

(source)

Varity_R

0.070

gMVP

0.22

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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