Genetic Variant ZBTB37:p.Arg213Pro (chr1-173870863-G-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_001122770.3(ZBTB37):c.638G>C(p.Arg213Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R213Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZBTB37
NM_001122770.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Publications

2 publications found

Variant links:

Genes affected

ZBTB37 (HGNC:28365): (zinc finger and BTB domain containing 37) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB37 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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB37	NM_001122770.3 link	c.638G>C	p.Arg213Pro	missense_variant	Exon 3 of 5	ENST00000367701.10	NP_001116242.1	Q5TC79-1B7Z7Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZBTB37	ENST00000367701.10 link	c.638G>C	p.Arg213Pro	missense_variant	Exon 3 of 5	1	NM_001122770.3	ENSP00000356674.4	Q5TC79-1
ZBTB37	ENST00000695459.1 link	c.638G>C	p.Arg213Pro	missense_variant	Exon 3 of 5			ENSP00000511931.1	Q5TC79-1
ZBTB37	ENST00000367702.1 link	c.638G>C	p.Arg213Pro	missense_variant	Exon 3 of 4	5		ENSP00000356675.1	Q5TC79-2
ZBTB37	ENST00000367704.5 link	c.638G>C	p.Arg213Pro	missense_variant	Exon 3 of 4	2		ENSP00000356677.1	Q5TC79-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251438

AF XY:

0.00000736

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0087

.;T;.;T

Eigen

Uncertain

0.64

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;.

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Benign

0.81

L;L;L;L

PhyloP100

9.3

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.69

N;N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.35

T;T;T;T

Polyphen

1.0, 1.0

.;D;D;D

Vest4

0.72

MutPred

0.49

Loss of MoRF binding (P = 0.0021);Loss of MoRF binding (P = 0.0021);Loss of MoRF binding (P = 0.0021);Loss of MoRF binding (P = 0.0021);

MVP

0.70

MPC

0.77

ClinPred

0.58

GERP RS

5.9

Varity_R

0.38

gMVP

0.66

Mutation Taster

=12/88

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over