NM_001316979.2:c.1398G>C

Variant names:

• chr19-58514192-C-G
• NM_001316979.2:c.1398G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001316979.2(ZBTB45):​c.1398G>C​(p.Lys466Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: ZBTB45 NM_001316979.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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]

ENSG00000307855 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316979.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB45	NM_001316979.2	MANE Select	c.1398G>C	p.Lys466Asn	missense	Exon 3 of 3	NP_001303908.1	Q96K62
	ZBTB45	NM_001316978.2		c.1398G>C	p.Lys466Asn	missense	Exon 3 of 3	NP_001303907.1	Q96K62
	ZBTB45	NM_001316981.2		c.1398G>C	p.Lys466Asn	missense	Exon 3 of 3	NP_001303910.1	Q96K62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB45	ENST00000594051.6	TSL:2 MANE Select	c.1398G>C	p.Lys466Asn	missense	Exon 3 of 3	ENSP00000469089.1	Q96K62
	ZBTB45	ENST00000354590.7	TSL:1	c.1398G>C	p.Lys466Asn	missense	Exon 3 of 3	ENSP00000346603.2	Q96K62
	ZBTB45	ENST00000869555.1		c.1485G>C	p.Lys495Asn	missense	Exon 4 of 4	ENSP00000539614.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460332 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726486

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111664

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.1
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.59		Loss of methylation at K466 (P = 0.0032)
MVP		0.48
MPC		2.7
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.72
gMVP		0.89
Mutation Taster		=28/72	disease causing

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

Other links and lift over

hg19: chr19-59025559;