3-42658840-C-G

Variant names:

• chr3-42658840-C-G
• NM_145166.4:c.485C>G

Variant summary

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

The NM_145166.4(ZBTB47):​c.485C>G​(p.Pro162Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000029 in 1,380,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ZBTB47 NM_145166.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.92

Genes affected

ZBTB47 (HGNC:26955): (zinc finger and BTB domain containing 47) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB47	NM_145166.4	c.485C>G	p.Pro162Arg	missense_variant	Exon 2 of 6	ENST00000232974.11	NP_660149.2
ZBTB47	NM_001410746.1	c.569C>G	p.Pro190Arg	missense_variant	Exon 2 of 6		NP_001397675.1
ZBTB47	XM_047449234.1	c.665C>G	p.Pro222Arg	missense_variant	Exon 3 of 7		XP_047305190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB47	ENST00000232974.11	c.485C>G	p.Pro162Arg	missense_variant	Exon 2 of 6	5	NM_145166.4	ENSP00000232974.6
ZBTB47	ENST00000680014.1	c.569C>G	p.Pro190Arg	missense_variant	Exon 2 of 6			ENSP00000504903.1
ZBTB47	ENST00000505904	c.-292C>G		5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000420968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1380726 Hom.: 0 Cov.: 32 AF XY: 0.00000587 AC XY: 4 AN XY: 680962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000509

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.485C>G (p.P162R) alteration is located in exon 2 (coding exon 1) of the ZBTB47 gene. This alteration results from a C to G substitution at nucleotide position 485, causing the proline (P) at amino acid position 162 to be replaced by an arginine (R). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Vest4		0.74
MutPred		0.36		Gain of glycosylation at Y163 (P = 0.0016);
MVP		0.25
MPC		1.3
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.63
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42700332;