14-104803442-T-C

Position:

• chr14-104803442-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001137601.3(ZBTB42):​c.*976T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 167,116 control chromosomes in the GnomAD database, including 59,819 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (53695 hom., cov: 33)
  • Exomes 𝑓: 0.90 (6124 hom.)
• Consequence: ZBTB42 NM_001137601.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB42	NM_001137601.3	c.*976T>C		3_prime_UTR_variant	1/1	ENST00000342537.8	NP_001131073.1
ZBTB42	NM_001370342.1	c.*976T>C		3_prime_UTR_variant	2/2		NP_001357271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB42	ENST00000342537.8	c.*976T>C		3_prime_UTR_variant	1/1	6	NM_001137601.3	ENSP00000409107.2

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126364 AN: 152024 Hom.: 53656 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.841

GnomAD4 exome AF: 0.904 AC: 13534 AN: 14972 Hom.: 6124 Cov.: 0 AF XY: 0.902 AC XY: 6476 AN XY: 7180

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.813

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.914

Gnomad4 OTH exome AF: 0.872

GnomAD4 genome AF: 0.831 AC: 126470 AN: 152144 Hom.: 53695 Cov.: 33 AF XY: 0.825 AC XY: 61361 AN XY: 74380

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.838

Alfa AF: 0.880 Hom.: 38906

Bravo AF: 0.820

Asia WGS AF: 0.508 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3803300; hg19: chr14-105269779; COSMIC: COSV61137322; COSMIC: COSV61137322;