Variant 1-173870416-A-G 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.191A>G(p.Asn64Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZBTB37
NM_001122770.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

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=0.121462405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB37	NM_001122770.3 linkuse as main transcript	c.191A>G	p.Asn64Ser	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.191A>G	p.Asn64Ser	missense_variant	3/5	1	NM_001122770.3	ENSP00000356674.4	Q5TC79-1
ZBTB37	ENST00000695459.1 linkuse as main transcript	c.191A>G	p.Asn64Ser	missense_variant	3/5			ENSP00000511931.1	Q5TC79-1
ZBTB37	ENST00000367702.1 linkuse as main transcript	c.191A>G	p.Asn64Ser	missense_variant	3/4	5		ENSP00000356675.1	Q5TC79-2
ZBTB37	ENST00000367704.5 linkuse as main transcript	c.191A>G	p.Asn64Ser	missense_variant	3/4	2		ENSP00000356677.1	Q5TC79-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251494

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135922

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 05, 2023

The c.191A>G (p.N64S) alteration is located in exon 3 (coding exon 1) of the ZBTB37 gene. This alteration results from a A to G substitution at nucleotide position 191, causing the asparagine (N) at amino acid position 64 to be replaced by a serine (S). 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

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.12

.;T;.;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.0033

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

D;D;D;.

M_CAP

Benign

0.0095

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.39

N;N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.050

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.99, 0.011

.;D;B;D

Vest4

0.13

MutPred

0.37

Loss of catalytic residue at N64 (P = 0.0265);Loss of catalytic residue at N64 (P = 0.0265);Loss of catalytic residue at N64 (P = 0.0265);Loss of catalytic residue at N64 (P = 0.0265);

MVP

0.62

MPC

0.27

ClinPred

0.40

GERP RS

4.4

Varity_R

0.22

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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