rs13011338

Variant names:

• chr2-218659366-C-T
• rs13011338
• NM_001379659.1:c.-362+3G>A

Variant summary

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

The NM_001379659.1(ZNF142):​c.-362+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 152,370 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (166 hom., cov: 32)
  • Exomes 𝑓: 0.075 (0 hom.)
• Consequence: ZNF142 NM_001379659.1 splice_region, intron
• Scores: Splicing: ADA: 0.001952
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=-0.47).
• 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 rank	MANE	Protein	UniProt
ZNF142	NM_001379659.1	c.-362+3G>A		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000411696.7	NP_001366588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF142	ENST00000411696.7	c.-362+3G>A		splice_region_variant, intron_variant	Intron 1 of 10	5	NM_001379659.1	ENSP00000398798.3

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6174 AN: 152132 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0425

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0383

GnomAD4 exome AF: 0.0750 AC: 9 AN: 120 Hom.: 0 Cov.: 0 AF XY: 0.0588 AC XY: 6 AN XY: 102

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0686

GnomAD4 genome AF: 0.0406 AC: 6178 AN: 152250 Hom.: 166 Cov.: 32 AF XY: 0.0397 AC XY: 2955 AN XY: 74434

Gnomad4 AFR AF: 0.0532

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0425

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0337

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0347 Hom.: 28

Bravo AF: 0.0414

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.024
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: rs13011338; hg19: chr2-219524089;