14-104801767-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001137601.3(ZBTB42):c.570G>A(p.Leu190=) variant causes a synonymous change. The variant allele was found at a frequency of 0.274 in 1,548,706 control chromosomes in the GnomAD database, including 59,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6127 hom., cov: 34)
  • Exomes 𝑓: 0.27 (53191 hom.)
• Consequence: ZBTB42 NM_001137601.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 14-104801767-G-A is Benign according to our data. Variant chr14-104801767-G-A is described in ClinVar as [Benign]. Clinvar id is 1260467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB42	NM_001137601.3	c.570G>A	p.Leu190=	synonymous_variant	1/1	ENST00000342537.8
ZBTB42	NM_001370342.1	c.570G>A	p.Leu190=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB42	ENST00000342537.8	c.570G>A	p.Leu190=	synonymous_variant	1/1		NM_001137601.3	P1
ZBTB42	ENST00000555360.1	c.570G>A	p.Leu190=	synonymous_variant	2/2	1		P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42125 AN: 152046 Hom.: 6116 Cov.: 34

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.242 AC: 36710 AN: 151526 Hom.: 4691 AF XY: 0.242 AC XY: 19521 AN XY: 80710

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.274 AC: 382272 AN: 1396542 Hom.: 53191 Cov.: 86 AF XY: 0.271 AC XY: 186906 AN XY: 688572

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.277 AC: 42172 AN: 152164 Hom.: 6127 Cov.: 34 AF XY: 0.275 AC XY: 20428 AN XY: 74388

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.266

Alfa AF: 0.247 Hom.: 1967

Bravo AF: 0.276

Asia WGS AF: 0.135 AC: 466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	9.5
Dann	Benign	0.81

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: rs10141867; hg19: chr14-105268104; COSMIC: COSV61137453;