7-73442246-T-C

Position:

• chr7-73442246-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1 PM2 PP2 BP4_Moderate

The NM_032408.4(BAZ1B):​c.4402A>G​(p.Ser1468Gly) 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. 15/21 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)
• Consequence: BAZ1B NM_032408.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

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 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity BAZ1B_HUMAN
• 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=0.078024626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAZ1B	NM_032408.4	c.4402A>G	p.Ser1468Gly	missense_variant	19/20	ENST00000339594.9
BAZ1B	NM_001370402.1	c.4402A>G	p.Ser1468Gly	missense_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAZ1B	ENST00000339594.9	c.4402A>G	p.Ser1468Gly	missense_variant	19/20	1	NM_032408.4	P1
BAZ1B	ENST00000404251.1	c.4402A>G	p.Ser1468Gly	missense_variant	19/19	2		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.4402A>G (p.S1468G) alteration is located in exon 19 (coding exon 19) of the BAZ1B gene. This alteration results from a A to G substitution at nucleotide position 4402, causing the serine (S) at amino acid position 1468 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	0.071
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.030
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	0.65	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.11
Sift	Benign	0.082	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0	B;B
Vest4		0.18
MutPred		0.15		Loss of phosphorylation at S1468 (P = 0.003);Loss of phosphorylation at S1468 (P = 0.003);
MVP		0.61
MPC		0.19
ClinPred		0.25	T
GERP RS		4.4
Varity_R		0.054
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-72856576;