19-58516644-G-T

Variant names:

• chr19-58516644-G-T
• rs1345364562
• NM_001316979.2:c.1030C>A

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.1030C>A​(p.Pro344Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P344S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB45 NM_001316979.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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=0.08729687).

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.1030C>A	p.Pro344Thr	missense	Exon 2 of 3	NP_001303908.1	Q96K62
	ZBTB45	NM_001316978.2		c.1030C>A	p.Pro344Thr	missense	Exon 2 of 3	NP_001303907.1	Q96K62
	ZBTB45	NM_001316981.2		c.1030C>A	p.Pro344Thr	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.1030C>A	p.Pro344Thr	missense	Exon 2 of 3	ENSP00000469089.1	Q96K62
	ZBTB45	ENST00000354590.7	TSL:1	c.1030C>A	p.Pro344Thr	missense	Exon 2 of 3	ENSP00000346603.2	Q96K62
	ZBTB45	ENST00000869555.1		c.1030C>A	p.Pro344Thr	missense	Exon 2 of 4	ENSP00000539614.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.067
Sift	Benign	0.48	T
Sift4G	Benign	0.54	T
Polyphen		0.079	B
Vest4		0.26
MutPred		0.43		Gain of phosphorylation at P344 (P = 0.002)
MVP		0.24
MPC		0.44
ClinPred		0.049	T
GERP RS		2.7
Varity_R		0.036
gMVP		0.26
Mutation Taster		=97/3	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

dbSNP: rs1345364562; hg19: chr19-59028011;