19-58516609-C-T

Variant names:

• chr19-58516609-C-T
• rs111742173
• NM_001316979.2:c.1065G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001316979.2(ZBTB45):​c.1065G>A​(p.Ala355Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,557,536 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (40 hom.)
• Consequence: ZBTB45 NM_001316979.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.94
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 19-58516609-C-T is Benign according to our data. Variant chr19-58516609-C-T is described in ClinVar as Benign. ClinVar VariationId is 780583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0151 (2283/151554) while in subpopulation AFR AF = 0.0496 (2047/41248). AF 95% confidence interval is 0.0478. There are 51 homozygotes in GnomAd4. There are 1088 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

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.1065G>A	p.Ala355Ala	synonymous	Exon 2 of 3	NP_001303908.1	Q96K62
	ZBTB45	NM_001316978.2		c.1065G>A	p.Ala355Ala	synonymous	Exon 2 of 3	NP_001303907.1	Q96K62
	ZBTB45	NM_001316981.2		c.1065G>A	p.Ala355Ala	synonymous	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.1065G>A	p.Ala355Ala	synonymous	Exon 2 of 3	ENSP00000469089.1	Q96K62
	ZBTB45	ENST00000354590.7	TSL:1	c.1065G>A	p.Ala355Ala	synonymous	Exon 2 of 3	ENSP00000346603.2	Q96K62
	ZBTB45	ENST00000869555.1		c.1065G>A	p.Ala355Ala	synonymous	Exon 2 of 4	ENSP00000539614.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2271 AN: 151438 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00768

Gnomad ASJ AF: 0.00606

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00815

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00555 AC: 1040 AN: 187526 AF XY: 0.00478

Gnomad AFR exome AF: 0.0550

Gnomad AMR exome AF: 0.00373

Gnomad ASJ exome AF: 0.00442

Gnomad EAS exome AF: 0.000124

Gnomad FIN exome AF: 0.000121

Gnomad NFE exome AF: 0.000612

Gnomad OTH exome AF: 0.00375

GnomAD4 exome AF: 0.00222 AC: 3117 AN: 1405982 Hom.: 40 Cov.: 33 AF XY: 0.00215 AC XY: 1494 AN XY: 693662

African (AFR) AF: 0.0516 AC: 1668 AN: 32324

American (AMR) AF: 0.00377 AC: 145 AN: 38436

Ashkenazi Jewish (ASJ) AF: 0.00422 AC: 95 AN: 22500

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38984

South Asian (SAS) AF: 0.00699 AC: 543 AN: 77714

European-Finnish (FIN) AF: 0.0000809 AC: 4 AN: 49452

Middle Eastern (MID) AF: 0.00433 AC: 18 AN: 4156

European-Non Finnish (NFE) AF: 0.000349 AC: 379 AN: 1084548

Other (OTH) AF: 0.00456 AC: 264 AN: 57868

GnomAD4 genome AF: 0.0151 AC: 2283 AN: 151554 Hom.: 51 Cov.: 32 AF XY: 0.0147 AC XY: 1088 AN XY: 74012

African (AFR) AF: 0.0496 AC: 2047 AN: 41248

American (AMR) AF: 0.00767 AC: 117 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00606 AC: 21 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00836 AC: 40 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10488

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67862

Other (OTH) AF: 0.0124 AC: 26 AN: 2102

Alfa AF: 0.00968 Hom.: 8

Bravo AF: 0.0173

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.43
DANN	Benign	0.87
PhyloP100		-1.9
Mutation Taster		=100/0	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: rs111742173; hg19: chr19-59027976; COSMIC: COSV99564766; COSMIC: COSV99564766;