6-36330593-T-C

Position:

• chr6-36330593-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010903.5(BNIP5):​c.98A>G​(p.Asp33Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BNIP5 NM_001010903.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.99

Genes affected

BNIP5 (HGNC:33769): (BCL2 interacting protein 5)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15921172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP5	NM_001010903.5	c.98A>G	p.Asp33Gly	missense_variant	2/12	ENST00000437635.3	NP_001010903.3
BNIP5	XM_011514596.3	c.98A>G	p.Asp33Gly	missense_variant	2/12		XP_011512898.1
BNIP5	XM_011514597.3	c.98A>G	p.Asp33Gly	missense_variant	2/12		XP_011512899.1
BNIP5	XM_011514598.3	c.-134-1879A>G		intron_variant			XP_011512900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP5	ENST00000437635.3	c.98A>G	p.Asp33Gly	missense_variant	2/12	1	NM_001010903.5	ENSP00000418983.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.98A>G (p.D33G) alteration is located in exon 2 (coding exon 1) of the C6orf222 gene. This alteration results from a A to G substitution at nucleotide position 98, causing the aspartic acid (D) at amino acid position 33 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.040
Sift	Benign	0.074	T
Sift4G	Benign	0.12	T
Polyphen		0.78	P
Vest4		0.43
MutPred		0.18		Gain of MoRF binding (P = 0.052);
MVP		0.19
MPC		0.083
ClinPred		0.75	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.036

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-36298370;