3-141443557-A-T

Variant names:

• chr3-141443557-A-T
• NM_001376113.1:c.1169A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001376113.1(ZBTB38):​c.1169A>T​(p.Glu390Val) 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: 32)
• Consequence: ZBTB38 NM_001376113.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

ZBTB38 (HGNC:26636): (zinc finger and BTB domain containing 38) The protein encoded by this gene is a zinc finger transcriptional activator that binds methylated DNA. The encoded protein can form homodimers or heterodimers through the zinc finger domains. In mouse, inhibition of this protein has been associated with apoptosis in some cell types. [provided by RefSeq, Jun 2010]

ENSG00000288585 (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_001376113.1. 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
	ZBTB38	NM_001376113.1	MANE Select	c.1169A>T	p.Glu390Val	missense	Exon 6 of 6	NP_001363042.1	Q8NAP3
	ZBTB38	NM_001080412.3		c.1169A>T	p.Glu390Val	missense	Exon 8 of 8	NP_001073881.2	Q8NAP3
	ZBTB38	NM_001350099.2		c.1169A>T	p.Glu390Val	missense	Exon 6 of 6	NP_001337028.1	Q8NAP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB38	ENST00000321464.7	TSL:6 MANE Select	c.1169A>T	p.Glu390Val	missense	Exon 6 of 6	ENSP00000372635.5	Q8NAP3
	ZBTB38	ENST00000509883.5	TSL:1	c.1169A>T	p.Glu390Val	missense	Exon 3 of 3	ENSP00000424254.1	D6RBC4
	ZBTB38	ENST00000441582.2	TSL:2	c.1169A>T	p.Glu390Val	missense	Exon 2 of 2	ENSP00000406955.2	Q8NAP3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.56		Gain of MoRF binding (P = 0.0106)
MVP		0.74
MPC		1.4
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.50
gMVP		0.37
Mutation Taster		=66/34	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: chr3-141162399;