chr19-58514227-C-T

Variant names:

• chr19-58514227-C-T
• NM_001316979.2:c.1363G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001316979.2(ZBTB45):​c.1363G>A​(p.Gly455Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZBTB45 NM_001316979.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57

Genes affected

ZBTB45 (HGNC:23715): (zinc finger and BTB domain containing 45) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB45	NM_001316979.2	c.1363G>A	p.Gly455Ser	missense_variant	Exon 3 of 3	ENST00000594051.6	NP_001303908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB45	ENST00000594051.6	c.1363G>A	p.Gly455Ser	missense_variant	Exon 3 of 3	2	NM_001316979.2	ENSP00000469089.1
ZBTB45	ENST00000354590.7	c.1363G>A	p.Gly455Ser	missense_variant	Exon 3 of 3	1		ENSP00000346603.2
ZBTB45	ENST00000600990.1	c.1363G>A	p.Gly455Ser	missense_variant	Exon 3 of 3	5		ENSP00000473072.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460254 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726434

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1363G>A (p.G455S) alteration is located in exon 3 (coding exon 2) of the ZBTB45 gene. This alteration results from a G to A substitution at nucleotide position 1363, causing the glycine (G) at amino acid position 455 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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Pathogenic	0.93	D
PROVEAN	Pathogenic	-5.4	D;.;.
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D;.;.
Sift4G	Benign	0.078	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.55
MutPred		0.58		Loss of catalytic residue at V456 (P = 0.1081);Loss of catalytic residue at V456 (P = 0.1081);Loss of catalytic residue at V456 (P = 0.1081);
MVP		0.67
MPC		2.5
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.64
gMVP		0.67

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: chr19-59025594;