chr3-42658819-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

ZBTB47 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000300878 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145166.4. 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
	ZBTB47	NM_145166.4	MANE Select	c.464A>C	p.Tyr155Ser	missense	Exon 2 of 6	NP_660149.2	Q9UFB7-1
	ZBTB47	NM_001410746.1		c.548A>C	p.Tyr183Ser	missense	Exon 2 of 6	NP_001397675.1	A0A7P0T820

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB47	ENST00000232974.11	TSL:5 MANE Select	c.464A>C	p.Tyr155Ser	missense	Exon 2 of 6	ENSP00000232974.6	Q9UFB7-1
	ZBTB47	ENST00000505904.1	TSL:5	c.-313A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000420968.1	D6RDG5
	ZBTB47	ENST00000680014.1		c.548A>C	p.Tyr183Ser	missense	Exon 2 of 6	ENSP00000504903.1	A0A7P0T820

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.1
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
PromoterAI		0.055	Neutral
Varity_R		0.74
gMVP		0.70
Mutation Taster		=75/25	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

hg19: chr3-42700311;