chr14-104803442-T-C

Variant names:

• chr14-104803442-T-C
• rs3803300
• NM_001137601.3:c.*976T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 50 publications found

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]

ZBTB42 Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 6

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001137601.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB42	NM_001137601.3	MANE Select	c.*976T>C		3_prime_UTR	Exon 1 of 1	NP_001131073.1
	ZBTB42	NM_001370342.1		c.*976T>C		3_prime_UTR	Exon 2 of 2	NP_001357271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB42	ENST00000342537.8	TSL:6 MANE Select	c.*976T>C		3_prime_UTR	Exon 1 of 1	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

African (AFR) AF: 0.750 AC: 9 AN: 12

American (AMR) AF: 0.700 AC: 7 AN: 10

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 0.357 AC: 5 AN: 14

South Asian (SAS) AF: 0.813 AC: 13 AN: 16

European-Finnish (FIN) AF: 0.905 AC: 13008 AN: 14378

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.914 AC: 402 AN: 440

Other (OTH) AF: 0.872 AC: 82 AN: 94

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

African (AFR) AF: 0.778 AC: 32281 AN: 41494

American (AMR) AF: 0.780 AC: 11925 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3081 AN: 3472

East Asian (EAS) AF: 0.330 AC: 1700 AN: 5148

South Asian (SAS) AF: 0.656 AC: 3168 AN: 4828

European-Finnish (FIN) AF: 0.909 AC: 9645 AN: 10616

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61855 AN: 67974

Other (OTH) AF: 0.838 AC: 1768 AN: 2110

Alfa AF: 0.873 Hom.: 149295

Bravo AF: 0.820

Asia WGS AF: 0.508 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.79
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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