Variant chr1-173870616-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001122770.3(ZBTB37):c.391G>A(p.Val131Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZBTB37
NM_001122770.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17155719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB37	NM_001122770.3 linkuse as main transcript	c.391G>A	p.Val131Met	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.391G>A	p.Val131Met	missense_variant	3/5	1	NM_001122770.3	ENSP00000356674.4	Q5TC79-1
ZBTB37	ENST00000695459.1 linkuse as main transcript	c.391G>A	p.Val131Met	missense_variant	3/5			ENSP00000511931.1	Q5TC79-1
ZBTB37	ENST00000367702.1 linkuse as main transcript	c.391G>A	p.Val131Met	missense_variant	3/4	5		ENSP00000356675.1	Q5TC79-2
ZBTB37	ENST00000367704.5 linkuse as main transcript	c.391G>A	p.Val131Met	missense_variant	3/4	2		ENSP00000356677.1	Q5TC79-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251326

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135868

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Dec 15, 2023

The c.391G>A (p.V131M) 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 391, causing the valine (V) at amino acid position 131 to be replaced by a methionine (M). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T;.;T

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D;D;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.34

N;N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.33

N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Benign

0.099

T;T;T;T

Polyphen

0.43, 0.94

.;B;P;B

Vest4

0.35

MutPred

0.31

Gain of disorder (P = 0.0994);Gain of disorder (P = 0.0994);Gain of disorder (P = 0.0994);Gain of disorder (P = 0.0994);

MVP

0.52

MPC

0.56

ClinPred

0.51

GERP RS

5.7

Varity_R

0.17

gMVP

0.40

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

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