chr2-218659583-G-A

Position:

• chr2-218659583-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001379659.1(ZNF142):​c.-576C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 152,316 control chromosomes in the GnomAD database, including 337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (337 hom., cov: 32)
  • Exomes 𝑓: 0.047 (0 hom.)
• Consequence: ZNF142 NM_001379659.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

Genes affected

ZNF142 (HGNC:12927): (zinc finger protein 142) The protein encoded by this gene belongs to the Kruppel family of C2H2-type zinc finger proteins. It contains 31 C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

BCS1L (HGNC:1020): (BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone) This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Several alternatively spliced transcripts encoding two different isoforms have been described. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-218659583-G-A is Benign according to our data. Variant chr2-218659583-G-A is described in ClinVar as [Benign]. Clinvar id is 1262585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF142	NM_001379659.1	c.-576C>T		5_prime_UTR_variant	1/11	ENST00000411696.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF142	ENST00000411696.7	c.-576C>T		5_prime_UTR_variant	1/11	5	NM_001379659.1	P1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8515 AN: 152112 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0312

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0437

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.0465 AC: 4 AN: 86 Hom.: 0 Cov.: 0 AF XY: 0.0690 AC XY: 4 AN XY: 58

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0286

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0560 AC: 8530 AN: 152230 Hom.: 337 Cov.: 32 AF XY: 0.0549 AC XY: 4088 AN XY: 74452

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0313

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0437

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0415 Hom.: 29

Bravo AF: 0.0588

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28384379; hg19: chr2-219524306;