Variant 1-173870763-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000367701.10(ZBTB37):c.538G>A(p.Ala180Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZBTB37
ENST00000367701.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037067026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB37	NM_001122770.3 linkuse as main transcript	c.538G>A	p.Ala180Thr	missense_variant	3/5	ENST00000367701.10	NP_001116242.1	Q5TC79-1B7Z7Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZBTB37	ENST00000367701.10 linkuse as main transcript	c.538G>A	p.Ala180Thr	missense_variant	3/5	1	NM_001122770.3	ENSP00000356674.4	Q5TC79-1
ZBTB37	ENST00000695459.1 linkuse as main transcript	c.538G>A	p.Ala180Thr	missense_variant	3/5			ENSP00000511931.1	Q5TC79-1
ZBTB37	ENST00000367702.1 linkuse as main transcript	c.538G>A	p.Ala180Thr	missense_variant	3/4	5		ENSP00000356675.1	Q5TC79-2
ZBTB37	ENST00000367704.5 linkuse as main transcript	c.538G>A	p.Ala180Thr	missense_variant	3/4	2		ENSP00000356677.1	Q5TC79-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251436

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS 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:

0.00000274

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.538G>A (p.A180T) alteration is located in exon 3 (coding exon 1) of the ZBTB37 gene. This alteration results from a G to A substitution at nucleotide position 538, causing the alanine (A) at amino acid position 180 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0067

.;T;.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.021

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T;T;.

M_CAP

Benign

0.0034

MetaRNN

Benign

0.037

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;N

MutationTaster

Benign

0.55

D;D;D;D;D

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.31

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.82

T;T;T;T

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.0

.;B;B;B

Vest4

0.031

MutPred

0.21

Gain of phosphorylation at A180 (P = 0.0419);Gain of phosphorylation at A180 (P = 0.0419);Gain of phosphorylation at A180 (P = 0.0419);Gain of phosphorylation at A180 (P = 0.0419);

MVP

0.27

MPC

0.32

ClinPred

0.20

GERP RS

4.9

Varity_R

0.054

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over