chr2-218658710-T-G

Variant names:

• chr2-218658710-T-G
• rs4674324
• ENST00000450765.5:n.-44A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000450765.5(ZNF142):​n.-44A>C variant causes a non coding transcript exon 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 ENST00000450765.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 12 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=-0.82).
• 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 rank	MANE	Protein	UniProt
ZNF142	NM_001379659.1	c.-44A>C		5_prime_UTR_variant	Exon 3 of 11	ENST00000411696.7	NP_001366588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF142	ENST00000411696.7	c.-44A>C		5_prime_UTR_variant	Exon 3 of 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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 6 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.656 AC: 21 AN: 32

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.148 AC: 6117 AN: 41456

American (AMR) AF: 0.553 AC: 8448 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2083 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4222 AN: 5150

South Asian (SAS) AF: 0.675 AC: 3251 AN: 4816

European-Finnish (FIN) AF: 0.572 AC: 6043 AN: 10560

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38960 AN: 67940

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.533 Hom.: 13658

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
PhyloP100		-1.1
PromoterAI		-0.031	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4674324; hg19: chr2-219523433;