chr8-80486812-TGTC-T

Variant names:

• chr8-80486812-TGTC-T
• rs144692080
• NM_001105539.3:c.5_7delCGT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_001105539.3(ZBTB10):​c.5_7delCGT​(p.Ser2del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,446,172 control chromosomes in the GnomAD database, including 1,665 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (205 hom., cov: 31)
  • Exomes 𝑓: 0.041 (1460 hom.)
• Consequence: ZBTB10 NM_001105539.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23
• Publications: 5 publications found

Genes affected

ZBTB10 (HGNC:30953): (zinc finger and BTB domain containing 10) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000251867 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001105539.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 8-80486812-TGTC-T is Benign according to our data. Variant chr8-80486812-TGTC-T is described in ClinVar as Benign. ClinVar VariationId is 1245018.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105539.3. 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
	ZBTB10	NM_001105539.3	MANE Select	c.5_7delCGT	p.Ser2del	disruptive_inframe_deletion	Exon 1 of 6	NP_001099009.1	Q96DT7-1
	ZBTB10	NM_023929.5		c.5_7delCGT	p.Ser2del	disruptive_inframe_deletion	Exon 1 of 7	NP_076418.3
	ZBTB10	NM_001277145.2		c.96+936_96+938delCGT		intron	N/A	NP_001264074.1	Q96DT7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB10	ENST00000455036.8	TSL:2 MANE Select	c.5_7delCGT	p.Ser2del	disruptive_inframe_deletion	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
	ZBTB10	ENST00000430430.5	TSL:5	c.5_7delCGT	p.Ser2del	disruptive_inframe_deletion	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
	ZBTB10	ENST00000961791.1		c.5_7delCGT	p.Ser2del	disruptive_inframe_deletion	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5326 AN: 149304 Hom.: 203 Cov.: 31

Gnomad AFR AF: 0.00685

Gnomad AMI AF: 0.00223

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0174

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.0746

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0327

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0372

GnomAD2 exomes AF: 0.0421 AC: 2741 AN: 65104 AF XY: 0.0432

Gnomad AFR exome AF: 0.00563

Gnomad AMR exome AF: 0.0138

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.0472

Gnomad NFE exome AF: 0.0357

Gnomad OTH exome AF: 0.0313

GnomAD4 exome AF: 0.0411 AC: 53240 AN: 1296754 Hom.: 1460 AF XY: 0.0415 AC XY: 26489 AN XY: 638174

African (AFR) AF: 0.00716 AC: 180 AN: 25136

American (AMR) AF: 0.0202 AC: 385 AN: 19038

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 339 AN: 21446

East Asian (EAS) AF: 0.158 AC: 4322 AN: 27320

South Asian (SAS) AF: 0.0704 AC: 4807 AN: 68278

European-Finnish (FIN) AF: 0.0506 AC: 2256 AN: 44594

Middle Eastern (MID) AF: 0.0413 AC: 154 AN: 3730

European-Non Finnish (NFE) AF: 0.0370 AC: 38315 AN: 1034428

Other (OTH) AF: 0.0470 AC: 2482 AN: 52784

GnomAD4 genome AF: 0.0356 AC: 5324 AN: 149418 Hom.: 205 Cov.: 31 AF XY: 0.0376 AC XY: 2743 AN XY: 72960

African (AFR) AF: 0.00683 AC: 279 AN: 40844

American (AMR) AF: 0.0234 AC: 352 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.0174 AC: 60 AN: 3450

East Asian (EAS) AF: 0.214 AC: 1069 AN: 5006

South Asian (SAS) AF: 0.0747 AC: 357 AN: 4782

European-Finnish (FIN) AF: 0.0515 AC: 505 AN: 9804

Middle Eastern (MID) AF: 0.0350 AC: 10 AN: 286

European-Non Finnish (NFE) AF: 0.0389 AC: 2614 AN: 67218

Other (OTH) AF: 0.0367 AC: 76 AN: 2070

Alfa AF: 0.0373 Hom.: 11

Bravo AF: 0.0327

Asia WGS AF: 0.122 AC: 417 AN: 3428

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=192/8	polymorphism (auto)

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: rs144692080; hg19: chr8-81399047; COSMIC: COSV66947550; COSMIC: COSV66947550;