rs764770791

Variant names:

• chr19-58516590-G-A
• rs764770791
• NM_001316979.2:c.1084C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001316979.2(ZBTB45):​c.1084C>T​(p.Pro362Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 1,571,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZBTB45 NM_001316979.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048778832).

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.1084C>T	p.Pro362Ser	missense	Exon 2 of 3	NP_001303908.1	Q96K62
	ZBTB45	NM_001316978.2		c.1084C>T	p.Pro362Ser	missense	Exon 2 of 3	NP_001303907.1	Q96K62
	ZBTB45	NM_001316981.2		c.1084C>T	p.Pro362Ser	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.1084C>T	p.Pro362Ser	missense	Exon 2 of 3	ENSP00000469089.1	Q96K62
	ZBTB45	ENST00000354590.7	TSL:1	c.1084C>T	p.Pro362Ser	missense	Exon 2 of 3	ENSP00000346603.2	Q96K62
	ZBTB45	ENST00000869555.1		c.1084C>T	p.Pro362Ser	missense	Exon 2 of 4	ENSP00000539614.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 4 AN: 199056 AF XY: 0.0000185

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000241

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1419566 Hom.: 0 Cov.: 32 AF XY: 0.00000285 AC XY: 2 AN XY: 702034

African (AFR) AF: 0.00 AC: 0 AN: 32628

American (AMR) AF: 0.00 AC: 0 AN: 39788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23436

East Asian (EAS) AF: 0.0000768 AC: 3 AN: 39084

South Asian (SAS) AF: 0.00 AC: 0 AN: 80352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091016

Other (OTH) AF: 0.00 AC: 0 AN: 58442

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000167 AC: 2

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	-0.47	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.79
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.68
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.022
Sift	Benign	0.66	T
Sift4G	Benign	1.0	T
Polyphen		0.067	B
Vest4		0.25
MutPred		0.27		Loss of loop (P = 0.0031)
MVP		0.22
MPC		0.37
ClinPred		0.020	T
GERP RS		3.0
Varity_R		0.033
gMVP		0.26
Mutation Taster		=91/9	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: rs764770791; hg19: chr19-59027957;