rs587780860

Variant names:

• chr2-218659756-A-G
• rs587780860
• ENST00000412366.5:c.-94A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001257344.2(BCS1L):​c.-94A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCS1L NM_001257344.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.764
• Publications: 0 publications found

Genes affected

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]

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]

ZNF142 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with impaired speech and hyperkinetic movements

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-218659756-A-G is Benign according to our data. Variant chr2-218659756-A-G is described in ClinVar as Benign. ClinVar VariationId is 136506.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257344.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCS1L	NM_001079866.2	MANE Select	c.-50+13A>G		intron	N/A	NP_001073335.1	Q9Y276
	BCS1L	NM_001257344.2		c.-94A>G		5_prime_UTR	Exon 1 of 8	NP_001244273.1	A0A024R445
	BCS1L	NM_001320717.2		c.-209A>G		5_prime_UTR	Exon 1 of 9	NP_001307646.1	Q9Y276

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCS1L	ENST00000412366.5	TSL:1	c.-94A>G		5_prime_UTR	Exon 1 of 8	ENSP00000406494.1	Q9Y276
	BCS1L	ENST00000359273.8	TSL:1 MANE Select	c.-50+13A>G		intron	N/A	ENSP00000352219.3	Q9Y276
	BCS1L	ENST00000392109.5	TSL:1	c.-232+13A>G		intron	N/A	ENSP00000375957.1	Q9Y276

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 194 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 144

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 16

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 146

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-0.76
PromoterAI		0.0024	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs587780860; hg19: chr2-219524479;