NM_001316979.2:c.880G>C

Variant names:

• chr19-58516794-C-G
• NM_001316979.2:c.880G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001316979.2(ZBTB45):​c.880G>C​(p.Glu294Gln) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E294K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB45 NM_001316979.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.73
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19574866).

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.880G>C	p.Glu294Gln	missense	Exon 2 of 3	NP_001303908.1	Q96K62
	ZBTB45	NM_001316978.2		c.880G>C	p.Glu294Gln	missense	Exon 2 of 3	NP_001303907.1	Q96K62
	ZBTB45	NM_001316981.2		c.880G>C	p.Glu294Gln	missense	Exon 2 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.880G>C	p.Glu294Gln	missense	Exon 2 of 3	ENSP00000469089.1	Q96K62
	ZBTB45	ENST00000354590.7	TSL:1	c.880G>C	p.Glu294Gln	missense	Exon 2 of 3	ENSP00000346603.2	Q96K62
	ZBTB45	ENST00000869555.1		c.880G>C	p.Glu294Gln	missense	Exon 2 of 4	ENSP00000539614.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.055
Sift	Uncertain	0.011	D
Sift4G	Benign	0.10	T
Polyphen		0.77	P
Vest4		0.30
MutPred		0.31		Loss of solvent accessibility (P = 0.0174)
MVP		0.42
MPC		0.46
ClinPred		0.36	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.28
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

hg19: chr19-59028161;