rs12878684

Variant names:

• chr14-104801242-A-G
• rs12878684
• NM_001137601.3:c.45A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001137601.3(ZBTB42):​c.45A>G​(p.Arg15Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,481,248 control chromosomes in the GnomAD database, including 573,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54257 hom., cov: 36)
  • Exomes 𝑓: 0.88 (519715 hom.)
• Consequence: ZBTB42 NM_001137601.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.42

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 14-104801242-A-G is Benign according to our data. Variant chr14-104801242-A-G is described in ClinVar as [Benign]. Clinvar id is 1246843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.42 with no splicing effect.
• 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 rank	MANE	Protein	UniProt
ZBTB42	NM_001137601.3	c.45A>G	p.Arg15Arg	synonymous_variant	Exon 1 of 1	ENST00000342537.8	NP_001131073.1
ZBTB42	NM_001370342.1	c.45A>G	p.Arg15Arg	synonymous_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.45A>G	p.Arg15Arg	synonymous_variant	Exon 1 of 1	6	NM_001137601.3	ENSP00000409107.2
ZBTB42	ENST00000555360.1	c.45A>G	p.Arg15Arg	synonymous_variant	Exon 2 of 2	1		ENSP00000450673.1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127114 AN: 152132 Hom.: 54214 Cov.: 36

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.841

GnomAD2 exomes AF: 0.766 AC: 68637 AN: 89556 AF XY: 0.771

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.870

Gnomad EAS exome AF: 0.304

Gnomad FIN exome AF: 0.895

Gnomad NFE exome AF: 0.907

Gnomad OTH exome AF: 0.829

GnomAD4 exome AF: 0.878 AC: 1167048 AN: 1328998 Hom.: 519715 Cov.: 68 AF XY: 0.874 AC XY: 568108 AN XY: 650036

African (AFR) AF: 0.785 AC: 22871 AN: 29152

American (AMR) AF: 0.724 AC: 19649 AN: 27158

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 18793 AN: 21442

East Asian (EAS) AF: 0.397 AC: 13733 AN: 34604

South Asian (SAS) AF: 0.697 AC: 48818 AN: 70012

European-Finnish (FIN) AF: 0.900 AC: 32359 AN: 35944

Middle Eastern (MID) AF: 0.804 AC: 4371 AN: 5436

European-Non Finnish (NFE) AF: 0.914 AC: 959879 AN: 1050046

Other (OTH) AF: 0.844 AC: 46575 AN: 55204

GnomAD4 genome AF: 0.836 AC: 127223 AN: 152250 Hom.: 54257 Cov.: 36 AF XY: 0.829 AC XY: 61693 AN XY: 74420

African (AFR) AF: 0.793 AC: 32970 AN: 41552

American (AMR) AF: 0.780 AC: 11939 AN: 15308

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

East Asian (EAS) AF: 0.328 AC: 1687 AN: 5142

South Asian (SAS) AF: 0.660 AC: 3190 AN: 4830

European-Finnish (FIN) AF: 0.909 AC: 9655 AN: 10626

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61880 AN: 68000

Other (OTH) AF: 0.838 AC: 1772 AN: 2114

Alfa AF: 0.873 Hom.: 10669

Bravo AF: 0.825

Asia WGS AF: 0.512 AC: 1782 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Lethal congenital contracture syndrome 6 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		2.4
PromoterAI		0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

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Other links and lift over

dbSNP: rs12878684; hg19: chr14-105267579; COSMIC: COSV61136985;