chr14-104801384-A-C

Position:

• chr14-104801384-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001137601.3(ZBTB42):​c.187A>C​(p.Thr63Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZBTB42 NM_001137601.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

Genes affected

ZBTB42 (HGNC:32550): (zinc finger and BTB domain containing 42) The protein encoded by this gene is a member of the C2H2 zinc finger protein family. This protein is predicted to have a pox virus and zinc finger (POZ) domain at the N-terminus and four zinc finger domains at the C-terminus. In human and mouse, the protein localizes to the nuclei of skeletal muscle cells. Knockdown of this gene in zebrafish results in abnormal skeletal muscle development and myofibrillar disorganization. A novel homozygous variant of the human gene has been associated with lethal congenital contracture syndrome, an autosomal recessive disorder that results in muscle wasting. [provided by RefSeq, Mar 2015]

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=0.25393367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB42	NM_001137601.3	c.187A>C	p.Thr63Pro	missense_variant	1/1	ENST00000342537.8
ZBTB42	NM_001370342.1	c.187A>C	p.Thr63Pro	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB42	ENST00000342537.8	c.187A>C	p.Thr63Pro	missense_variant	1/1		NM_001137601.3	P1
ZBTB42	ENST00000555360.1	c.187A>C	p.Thr63Pro	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 90

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.187A>C (p.T63P) alteration is located in exon 2 (coding exon 1) of the ZBTB42 gene. This alteration results from a A to C substitution at nucleotide position 187, causing the threonine (T) at amino acid position 63 to be replaced by a proline (P). 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	0.46
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T;T
Eigen	Benign	-0.000076
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.17	.;T
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	0.70	N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.19
Sift	Benign	0.061	T;T
Sift4G	Uncertain	0.057	T;T
Polyphen		0.92	P;P
Vest4		0.15
MutPred		0.59		Gain of catalytic residue at A58 (P = 0);Gain of catalytic residue at A58 (P = 0);
MVP		0.20
ClinPred		0.28	T
GERP RS		1.7
Varity_R		0.36

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: chr14-105267721;