rs1368607213

Positions:

• chr14-104802228-C-G
• chr14-104802228-C-T

Variant summary

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

The NM_001137601.3(ZBTB42):​c.1031C>G​(p.Ser344Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,397,804 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZBTB42 NM_001137601.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB42	NM_001137601.3	c.1031C>G	p.Ser344Trp	missense_variant	1/1	ENST00000342537.8	NP_001131073.1
ZBTB42	NM_001370342.1	c.1031C>G	p.Ser344Trp	missense_variant	2/2		NP_001357271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB42	ENST00000342537.8	c.1031C>G	p.Ser344Trp	missense_variant	1/1	6	NM_001137601.3	ENSP00000409107.2
ZBTB42	ENST00000555360.1	c.1031C>G	p.Ser344Trp	missense_variant	2/2	1		ENSP00000450673.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397804 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 689390

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.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.59
MutPred		0.40		Gain of catalytic residue at K341 (P = 2e-04);Gain of catalytic residue at K341 (P = 2e-04);
MVP		0.23
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.59

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

LitVar

Other links and lift over

dbSNP: rs1368607213; hg19: chr14-105268565;