7-73442504-G-A

Position:

• chr7-73442504-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_032408.4(BAZ1B):​c.4144C>T​(p.His1382Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: BAZ1B NM_032408.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49

Genes affected

BAZ1B (HGNC:961): (bromodomain adjacent to zinc finger domain 1B) This gene encodes a member of the bromodomain protein family. The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, BAZ1B
• BP4: Computational evidence support a benign effect (MetaRNN=0.36151212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ1B	NM_032408.4	c.4144C>T	p.His1382Tyr	missense_variant	19/20	ENST00000339594.9
BAZ1B	NM_001370402.1	c.4144C>T	p.His1382Tyr	missense_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ1B	ENST00000339594.9	c.4144C>T	p.His1382Tyr	missense_variant	19/20	1	NM_032408.4	P1
BAZ1B	ENST00000404251.1	c.4144C>T	p.His1382Tyr	missense_variant	19/19	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

BAZ1B-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 15, 2023

The BAZ1B c.4144C>T variant is predicted to result in the amino acid substitution p.His1382Tyr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.94	L;L
MutationTaster	Benign	0.53	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.071
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.031	D;D
Polyphen		0.66	P;P
Vest4		0.31
MutPred		0.53		Loss of catalytic residue at I1380 (P = 0.1618);Loss of catalytic residue at I1380 (P = 0.1618);
MVP		0.26
MPC		0.31
ClinPred		0.49	T
GERP RS		5.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.086
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-72856834;