rs572418952

Variant names:

• chr10-131981785-C-A
• rs572418952
• NM_004052.4:c.22G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-131981785-C-A
• chr10-131981785-C-T

Variant summary

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

The NM_004052.4(BNIP3):​c.22G>T​(p.Gly8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G8V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: BNIP3 NM_004052.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 0 publications found

Genes affected

BNIP3 (HGNC:1084): (BCL2 interacting protein 3) This gene is encodes a mitochondrial protein that contains a BH3 domain and acts as a pro-apoptotic factor. The encoded protein interacts with anti-apoptotic proteins, including the E1B 19 kDa protein and Bcl2. This gene is silenced in tumors by DNA methylation. [provided by RefSeq, Dec 2014]

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=0.23421702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004052.4. 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
	BNIP3	NM_004052.4	MANE Select	c.22G>T	p.Gly8Trp	missense	Exon 1 of 6	NP_004043.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BNIP3	ENST00000368636.9	TSL:1 MANE Select	c.22G>T	p.Gly8Trp	missense	Exon 1 of 6	ENSP00000357625.6	Q12983
	BNIP3	ENST00000540159.4	TSL:1	c.22G>T	p.Gly8Trp	missense	Exon 1 of 5	ENSP00000446145.3	B4DHJ7
	BNIP3	ENST00000924284.1		c.22G>T	p.Gly8Trp	missense	Exon 1 of 7	ENSP00000594343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331308 Hom.: 0 Cov.: 32 AF XY: 0.00000152 AC XY: 1 AN XY: 656866

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27342

American (AMR) AF: 0.00 AC: 0 AN: 28744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23510

East Asian (EAS) AF: 0.00 AC: 0 AN: 29128

South Asian (SAS) AF: 0.00 AC: 0 AN: 73110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4186

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1055322

Other (OTH) AF: 0.00 AC: 0 AN: 55136

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.083
PrimateAI	Uncertain	0.75	T
REVEL	Benign	0.19
Sift4G	Uncertain	0.0060	D
Vest4		0.28
MVP		0.33
MPC		1.1
ClinPred		0.75	D
GERP RS		1.3
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.064
gMVP		0.18
Mutation Taster		=91/9	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: rs572418952; hg19: chr10-133795289;