3-42658819-A-C

Variant names:

• chr3-42658819-A-C
• NM_145166.4:c.464A>C

Variant summary

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

The NM_145166.4(ZBTB47):​c.464A>C​(p.Tyr155Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB47 NM_145166.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12

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.464A>C	p.Tyr155Ser	missense_variant	Exon 2 of 6	ENST00000232974.11	NP_660149.2
ZBTB47	NM_001410746.1	c.548A>C	p.Tyr183Ser	missense_variant	Exon 2 of 6		NP_001397675.1
ZBTB47	XM_047449234.1	c.644A>C	p.Tyr215Ser	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.464A>C	p.Tyr155Ser	missense_variant	Exon 2 of 6	5	NM_145166.4	ENSP00000232974.6
ZBTB47	ENST00000505904	c.-313A>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	5		ENSP00000420968.1
ZBTB47	ENST00000680014.1	c.548A>C	p.Tyr183Ser	missense_variant	Exon 2 of 6			ENSP00000504903.1
ZBTB47	ENST00000505904	c.-313A>C		5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000420968.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 12, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.011
Eigen_PC	Benign	-0.084
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Uncertain	0.098	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.60
MutPred		0.60		Loss of helix (P = 0.0068);
MVP		0.14
MPC		1.5
ClinPred		0.99	D
GERP RS		2.1
Varity_R		0.74
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42700311;