chr8-80487049-C-T

Variant names:

• chr8-80487049-C-T
• rs772027446
• NM_001105539.3:c.239C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001105539.3(ZBTB10):​c.239C>T​(p.Ser80Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000883 in 1,517,650 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000091 (1 hom.)
• Consequence: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.947
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005872071).

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.239C>T	p.Ser80Phe	missense	Exon 1 of 6	NP_001099009.1	Q96DT7-1
	ZBTB10	NM_023929.5		c.239C>T	p.Ser80Phe	missense	Exon 1 of 7	NP_076418.3
	ZBTB10	NM_001277145.2		c.96+1170C>T		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.239C>T	p.Ser80Phe	missense	Exon 1 of 6	ENSP00000412036.3	Q96DT7-1
	ZBTB10	ENST00000430430.5	TSL:5	c.239C>T	p.Ser80Phe	missense	Exon 2 of 7	ENSP00000387462.1	Q96DT7-1
	ZBTB10	ENST00000961791.1		c.239C>T	p.Ser80Phe	missense	Exon 2 of 7	ENSP00000631850.1

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151836 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: 0.00175

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000173 AC: 19 AN: 109640 AF XY: 0.000163

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00263

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000908 AC: 124 AN: 1365702 Hom.: 1 Cov.: 34 AF XY: 0.0000994 AC XY: 67 AN XY: 673936

African (AFR) AF: 0.00 AC: 0 AN: 28096

American (AMR) AF: 0.00 AC: 0 AN: 33258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24238

East Asian (EAS) AF: 0.00369 AC: 122 AN: 33020

South Asian (SAS) AF: 0.00 AC: 0 AN: 77550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5382

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071664

Other (OTH) AF: 0.00 AC: 0 AN: 57010

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 151948 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00176 AC: 9 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67960

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000638 AC: 1

Asia WGS AF: 0.000870 AC: 3 AN: 3462

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	0.22
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.95
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.085
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.25	T
Polyphen		0.35	B
Vest4		0.16
MutPred		0.18		Loss of glycosylation at S80 (P = 0.0046)
MVP		0.043
MPC		0.98
ClinPred		0.25	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.11
Mutation Taster		=96/4	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: rs772027446; hg19: chr8-81399284; COSMIC: COSV105933808; COSMIC: COSV105933808;