NM_001379659.1:c.-362+3G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

BCS1L Gene-Disease associations (from GenCC):

• Bjornstad syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics, ClinGen, G2P
• GRACILE syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• Leigh syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, ClinGen
• mitochondrial complex III deficiency nuclear type 1

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mitochondrial complex III deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal tubulopathy-encephalopathy-liver failure syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379659.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF142	NM_001379659.1	MANE Select	c.-362+3G>A		splice_region intron	N/A	NP_001366588.1
	ZNF142	NM_001366290.3		c.-597G>A		5_prime_UTR	Exon 1 of 10	NP_001353219.1
	ZNF142	NM_001366291.2		c.-597G>A		5_prime_UTR	Exon 1 of 9	NP_001353220.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF142	ENST00000411696.7	TSL:5 MANE Select	c.-362+3G>A		splice_region intron	N/A	ENSP00000398798.3
	ZNF142	ENST00000449707.5	TSL:1	c.-267+3G>A		splice_region intron	N/A	ENSP00000408643.1
	ZNF142	ENST00000450765.5	TSL:1	n.-362+3G>A		splice_region intron	N/A	ENSP00000397456.1

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.125 AC: 1 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0686 AC: 7 AN: 102

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0532 AC: 2210 AN: 41548

American (AMR) AF: 0.0227 AC: 347 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.118 AC: 606 AN: 5154

South Asian (SAS) AF: 0.0425 AC: 205 AN: 4824

European-Finnish (FIN) AF: 0.0273 AC: 290 AN: 10622

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0337 AC: 2290 AN: 68012

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0348 Hom.: 37

Bravo AF: 0.0414

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		1.1
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=80/20	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13011338; hg19: chr2-219524089;