5-173151681-C-G

Variant names:

• chr5-173151681-C-G
• rs959443880
• ENST00000231668.13:c.293C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013979.3(BNIP1):​c.293C>G​(p.Pro98Arg) variant causes a missense 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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P98L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNIP1 NM_013979.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167
• Publications: 0 publications found

Genes affected

BNIP1 (HGNC:1082): (BCL2 interacting protein 1) This gene is a member of the BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family. It interacts with the E1B 19 kDa protein, which protects cells from virally-induced cell death. The encoded protein also interacts with E1B 19 kDa-like sequences of BCL2, another apoptotic protector. In addition, this protein is involved in vesicle transport into the endoplasmic reticulum. Alternative splicing of this gene results in four protein products with identical N- and C-termini. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13915896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013979.3. 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
	BNIP1	NM_001205.3	MANE Select	c.178-2641C>G		intron	N/A	NP_001196.2	Q12981-4
	BNIP1	NM_013979.3		c.293C>G	p.Pro98Arg	missense	Exon 3 of 7	NP_053582.2	Q12981-1
	BNIP1	NM_013980.3		c.293C>G	p.Pro98Arg	missense	Exon 3 of 6	NP_053583.2	Q12981-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP1	ENST00000231668.13	TSL:1	c.293C>G	p.Pro98Arg	missense	Exon 3 of 7	ENSP00000231668.9	Q12981-1
	BNIP1	ENST00000352523.10	TSL:1	c.293C>G	p.Pro98Arg	missense	Exon 3 of 6	ENSP00000239214.8	Q12981-3
	BNIP1	ENST00000351486.10	TSL:1 MANE Select	c.178-2641C>G		intron	N/A	ENSP00000239215.7	Q12981-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.0
DANN	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.17
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.039
Sift	Benign	0.084	T
Sift4G	Uncertain	0.048	D
Polyphen		0.87	P
Vest4		0.14
MutPred		0.23		Loss of loop (P = 0.0603)
MVP		0.43
MPC		0.33
ClinPred		0.094	T
GERP RS		1.4
gMVP		0.066
Mutation Taster		=99/1	polymorphism

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: rs959443880; hg19: chr5-172578684;