14-104801835-G-A

Variant names:

• chr14-104801835-G-A
• NM_001137601.3:c.638G>A

Variant summary

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

The NM_001137601.3(ZBTB42):​c.638G>A​(p.Ser213Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,397,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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.)
• Consequence: ZBTB42 NM_001137601.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.93

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=0.107289374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB42	NM_001137601.3	c.638G>A	p.Ser213Asn	missense_variant	Exon 1 of 1	ENST00000342537.8	NP_001131073.1
ZBTB42	NM_001370342.1	c.638G>A	p.Ser213Asn	missense_variant	Exon 2 of 2		NP_001357271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB42	ENST00000342537.8	c.638G>A	p.Ser213Asn	missense_variant	Exon 1 of 1	6	NM_001137601.3	ENSP00000409107.2
ZBTB42	ENST00000555360.1	c.638G>A	p.Ser213Asn	missense_variant	Exon 2 of 2	1		ENSP00000450673.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397806 Hom.: 0 Cov.: 85 AF XY: 0.00000145 AC XY: 1 AN XY: 689408

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	0.28
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0083	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.41	.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.10
Sift	Benign	0.29	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.048	B;B
Vest4		0.060
MutPred		0.29		Gain of catalytic residue at R215 (P = 0.0036);Gain of catalytic residue at R215 (P = 0.0036);
MVP		0.014
ClinPred		0.44	T
GERP RS		3.2
Varity_R		0.099

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: chr14-105268172;