Variant 1-173871112-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001122770.3(ZBTB37):c.887C>G(p.Ala296Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ZBTB37
NM_001122770.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

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:

Genome browser will be placed here

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=0.026902437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB37	NM_001122770.3 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	3/5	ENST00000367701.10	NP_001116242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB37	ENST00000367701.10 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	3/5	1	NM_001122770.3	ENSP00000356674	P1	Q5TC79-1
ZBTB37	ENST00000695459.1 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	3/5			ENSP00000511931	P1	Q5TC79-1
ZBTB37	ENST00000367702.1 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	3/4	5		ENSP00000356675		Q5TC79-2
ZBTB37	ENST00000367704.5 linkuse as main transcript	c.887C>G	p.Ala296Gly	missense_variant	3/4	2		ENSP00000356677		Q5TC79-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000530

AC:

AN:

245446

Hom.:

AF XY:

0.0000829

AC XY:

AN XY:

132670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000671

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1459616

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725816

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000577

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

Jun 07, 2023

The c.887C>G (p.A296G) alteration is located in exon 3 (coding exon 1) of the ZBTB37 gene. This alteration results from a C to G substitution at nucleotide position 887, causing the alanine (A) at amino acid position 296 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0048

.;T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

T;T;T;.

M_CAP

Benign

0.0047

MetaRNN

Benign

0.027

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Benign

0.36

PROVEAN

Benign

0.50

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.010, 0.0

.;B;B;B

Vest4

0.25

MutPred

0.23

Loss of stability (P = 0.0215);Loss of stability (P = 0.0215);Loss of stability (P = 0.0215);Loss of stability (P = 0.0215);

MVP

0.38

MPC

0.33

ClinPred

0.18

GERP RS

6.2

Varity_R

0.11

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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