chr8-80486950-C-A

Position:

• chr8-80486950-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105539.3(ZBTB10):​c.140C>A​(p.Pro47His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,362,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: ZBTB10 NM_001105539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.455

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19245043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB10	NM_001105539.3	c.140C>A	p.Pro47His	missense_variant	1/6	ENST00000455036.8	NP_001099009.1
ZBTB10	NM_023929.5	c.140C>A	p.Pro47His	missense_variant	1/7		NP_076418.3
ZBTB10	NM_001277145.2	c.96+1071C>A		intron_variant			NP_001264074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB10	ENST00000455036.8	c.140C>A	p.Pro47His	missense_variant	1/6	2	NM_001105539.3	ENSP00000412036.3
ZBTB10	ENST00000430430.5	c.140C>A	p.Pro47His	missense_variant	2/7	5		ENSP00000387462.1
ZBTB10	ENST00000426744.5	c.140C>A	p.Pro47His	missense_variant	1/7	5		ENSP00000416134.2
ZBTB10	ENST00000379091.8	c.96+1071C>A		intron_variant		2		ENSP00000368384.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000661 AC: 9 AN: 1362274 Hom.: 0 Cov.: 34 AF XY: 0.00000893 AC XY: 6 AN XY: 671872

Gnomad4 AFR exome AF: 0.0000359

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000749

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.140C>A (p.P47H) alteration is located in exon 1 (coding exon 1) of the ZBTB10 gene. This alteration results from a C to A substitution at nucleotide position 140, causing the proline (P) at amino acid position 47 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.57	.;T;T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.42	N;N;N
REVEL	Benign	0.038
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		0.78	P;P;P
Vest4		0.31
MutPred		0.20		Loss of glycosylation at P47 (P = 0.005);Loss of glycosylation at P47 (P = 0.005);Loss of glycosylation at P47 (P = 0.005);
MVP		0.043
MPC		0.85
ClinPred		0.28	T
GERP RS		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs573842562; hg19: chr8-81399185;