3-42658762-C-T

Variant names:

• chr3-42658762-C-T
• rs1710670079
• NM_145166.4:c.407C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP6

The NM_145166.4(ZBTB47):​c.407C>T​(p.Pro136Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000029 in 1,378,912 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ZBTB47 NM_145166.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 4.13

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34923154).
• BP6: Variant 3-42658762-C-T is Benign according to our data. Variant chr3-42658762-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1686386.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB47	NM_145166.4	c.407C>T	p.Pro136Leu	missense_variant	Exon 2 of 6	ENST00000232974.11	NP_660149.2
ZBTB47	NM_001410746.1	c.491C>T	p.Pro164Leu	missense_variant	Exon 2 of 6		NP_001397675.1
ZBTB47	XM_047449234.1	c.587C>T	p.Pro196Leu	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.407C>T	p.Pro136Leu	missense_variant	Exon 2 of 6	5	NM_145166.4	ENSP00000232974.6
ZBTB47	ENST00000680014.1	c.491C>T	p.Pro164Leu	missense_variant	Exon 2 of 6			ENSP00000504903.1
ZBTB47	ENST00000505904.1	c.-370C>T		upstream_gene_variant		5		ENSP00000420968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1378912 Hom.: 0 Cov.: 32 AF XY: 0.00000294 AC XY: 2 AN XY: 679828

Gnomad4 AFR exome AF: 0.0000317

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: 0.00000279

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1 Benign:1

May 04, 2022

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.407C>T (p.P136L) alteration is located in exon 2 (coding exon 1) of the ZBTB47 gene. This alteration results from a C to T substitution at nucleotide position 407, causing the proline (P) at amino acid position 136 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.017
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.021	D
Vest4		0.37
MutPred		0.56		Gain of glycosylation at Y139 (P = 0.0053);
MVP		0.21
MPC		1.0
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.098
gMVP		0.24

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: rs1710670079; hg19: chr3-42700254;