Genetic Variant BAZ1A:p.Glu23Gln (chr14-34874538-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_013448.3(BAZ1A):c.67G>C(p.Glu23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,459,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

BAZ1A
NM_013448.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

BAZ1A (HGNC:960): (bromodomain adjacent to zinc finger domain 1A) The BAZ1A gene encodes the accessory subunit of the ATP-dependent chromatin assembly factor (ACF), a member of the ISWI ('imitation switch') family of chromatin remodeling complexes (summarized by Racki et al., 2009 [PubMed 20033039]).[supplied by OMIM, Apr 2010]

BAZ1A links:

BAZ1A-AS1 (HGNC:55440): (BAZ1A antisense RNA 1)

BAZ1A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26579326).

BS2

High AC in GnomAdExome4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAZ1A	NM_013448.3 link	c.67G>C	p.Glu23Gln	missense_variant	Exon 2 of 27	ENST00000360310.6	NP_038476.2	Q9NRL2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BAZ1A	ENST00000360310.6 link	c.67G>C	p.Glu23Gln	missense_variant	Exon 2 of 27	1	NM_013448.3	ENSP00000353458.1	Q9NRL2-1
BAZ1A	ENST00000382422.6 link	c.67G>C	p.Glu23Gln	missense_variant	Exon 1 of 26	1		ENSP00000371859.2	Q9NRL2-1
BAZ1A	ENST00000358716.8 link	c.67G>C	p.Glu23Gln	missense_variant	Exon 2 of 26	1		ENSP00000351555.4	Q9NRL2-2
BAZ1A-AS1	ENST00000557373.1 link	n.196C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248534

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134846

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1459792

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726248

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:

0.0000369

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.67G>C (p.E23Q) alteration is located in exon 2 (coding exon 1) of the BAZ1A gene. This alteration results from a G to C substitution at nucleotide position 67, causing the glutamic acid (E) at amino acid position 23 to be replaced by a glutamine (Q). 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

0.38

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.058

.;T;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.88

D;.;D

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.091

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.13

B;B;B

Vest4

0.33

MutPred

0.62

Gain of ubiquitination at K28 (P = 0.0773);Gain of ubiquitination at K28 (P = 0.0773);Gain of ubiquitination at K28 (P = 0.0773);

MVP

0.60

MPC

0.30

ClinPred

0.23

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.59

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