rs4674324

Positions:

• chr2-218658710-T-G

Variant summary

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

The NM_001379659.1(ZNF142):​c.-44A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,980 control chromosomes in the GnomAD database, including 19,787 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 0.47 (19787 hom., cov: 31)
  • Exomes 𝑓: 0.65 (10 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF142 NM_001379659.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF142	NM_001379659.1	c.-44A>C		5_prime_UTR_variant	3/11	ENST00000411696.7	NP_001366588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF142	ENST00000411696.7	c.-44A>C		5_prime_UTR_variant	3/11	5	NM_001379659.1	ENSP00000398798.3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70987 AN: 151862 Hom.: 19788 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.520

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.646 AC: 31 AN: 48 Hom.: 10 Cov.: 0 AF XY: 0.594 AC XY: 19 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.656

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.467 AC: 70978 AN: 151980 Hom.: 19787 Cov.: 31 AF XY: 0.475 AC XY: 35287 AN XY: 74290

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.520

Alfa AF: 0.540 Hom.: 8973

Bravo AF: 0.449

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4674324; hg19: chr2-219523433;