chr14-77268506-C-A

Position:

• chr14-77268506-C-A

Variant summary

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

The NM_021257.4(NGB):​c.281G>T​(p.Arg94Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NGB NM_021257.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.276

Genes affected

NGB (HGNC:14077): (neuroglobin) This gene encodes an oxygen-binding protein that is distantly related to members of the globin gene family. It is highly conserved among other vertebrates. It is expressed in the central and peripheral nervous system where it may be involved in increasing oxygen availability and providing protection under hypoxic/ischemic conditions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGB	NM_021257.4	c.281G>T	p.Arg94Met	missense_variant	3/4	ENST00000298352.5	NP_067080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGB	ENST00000298352.5	c.281G>T	p.Arg94Met	missense_variant	3/4	1	NM_021257.4	ENSP00000298352	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 10, 2023

The c.281G>T (p.R94M) alteration is located in exon 3 (coding exon 3) of the NGB gene. This alteration results from a G to T substitution at nucleotide position 281, causing the arginine (R) at amino acid position 94 to be replaced by a methionine (M). 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	0.33
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.015	D
Polyphen		0.97	D
Vest4		0.40
MutPred		0.54		Loss of MoRF binding (P = 0.0362);
MVP		0.89
MPC		0.25
ClinPred		0.92	D
GERP RS		-0.30
Varity_R		0.34
gMVP		0.42

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: chr14-77734849;