rs1055806

Variant names:

• chr8-26391347-G-T
• rs1055806
• NM_004331.3:c.205G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004331.3(BNIP3L):​c.205G>T​(p.Gly69*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNIP3L NM_004331.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.04
• Publications: 4 publications found

Genes affected

BNIP3L (HGNC:1085): (BCL2 interacting protein 3 like) This gene encodes a protein that belongs to the pro-apoptotic subfamily within the Bcl-2 family of proteins. The encoded protein binds to Bcl-2 and possesses the BH3 domain. The protein directly targets mitochondria and causes apoptotic changes, including loss of membrane potential and the release of cytochrome c. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004331.3. 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
	BNIP3L	NM_004331.3	MANE Select	c.205G>T	p.Gly69*	stop_gained	Exon 2 of 6	NP_004322.1
	BNIP3L	NM_001330491.2		c.85G>T	p.Gly29*	stop_gained	Exon 2 of 6	NP_001317420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP3L	ENST00000380629.7	TSL:1 MANE Select	c.205G>T	p.Gly69*	stop_gained	Exon 2 of 6	ENSP00000370003.2
	BNIP3L	ENST00000520077.5	TSL:1	n.100+8117G>T		intron	N/A	ENSP00000428919.1
	BNIP3L	ENST00000523949.5	TSL:3	c.139G>T	p.Gly47*	stop_gained	Exon 2 of 6	ENSP00000429171.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.000133 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	40
DANN	Uncertain	0.99
Eigen	Pathogenic	1.2
Eigen_PC	Pathogenic	1.1
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		8.0
Vest4		0.91
GERP RS		5.0
Mutation Taster		=4/196	disease causing (fs/PTC)

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: rs1055806; hg19: chr8-26248863;