14-104801891-G-C

Position:

• chr14-104801891-G-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.694G>C​(p.Glu232Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZBTB42 NM_001137601.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.95

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=0.24161008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB42	NM_001137601.3	c.694G>C	p.Glu232Gln	missense_variant	1/1	ENST00000342537.8	NP_001131073.1
ZBTB42	NM_001370342.1	c.694G>C	p.Glu232Gln	missense_variant	2/2		NP_001357271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB42	ENST00000342537.8	c.694G>C	p.Glu232Gln	missense_variant	1/1	6	NM_001137601.3	ENSP00000409107.2
ZBTB42	ENST00000555360.1	c.694G>C	p.Glu232Gln	missense_variant	2/2	1		ENSP00000450673.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.16e-7 AC: 1 AN: 1396372 Hom.: 0 Cov.: 77 AF XY: 0.00000145 AC XY: 1 AN XY: 688802

Gnomad4 AFR exome AF: 0.00

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	0.080
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	.;T
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.16
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.34	T;T
Polyphen		0.99	D;D
Vest4		0.059
MutPred		0.22		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.030
ClinPred		0.86	D
GERP RS		3.7
Varity_R		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4983387; hg19: chr14-105268228;