Variant 17-49506655-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002507.4(NGFR):c.565G>C(p.Glu189Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,365,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

NGFR
NM_002507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Variant links:

Genes affected

NGFR (HGNC:7809): (nerve growth factor receptor) Nerve growth factor receptor contains an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions followed by a serine/threonine-rich region, a single transmembrane domain, and a 155-amino acid cytoplasmic domain. The cysteine-rich region contains the nerve growth factor binding domain. [provided by RefSeq, Jul 2008]

NGFR links:

NGFR-AS1 (HGNC:55555): (NGFR antisense RNA 1)

NGFR-AS1 links:

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ACMG classification

Classification made for transcript

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=0.18603322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGFR	NM_002507.4 link	c.565G>C	p.Glu189Gln	missense_variant	3/6	ENST00000172229.8	NP_002498.1	P08138-1
NGFR-AS1	NR_103773.1 link	n.378-155C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NGFR	ENST00000172229.8 link	c.565G>C	p.Glu189Gln	missense_variant	3/6	1	NM_002507.4	ENSP00000172229.3	P08138-1
NGFR	ENST00000504201.1 link	c.283G>C	p.Glu95Gln	missense_variant	3/6	2		ENSP00000421731.1	P08138-2
NGFR-AS1	ENST00000514506.1 link	n.378-155C>G		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1365846

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

669122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000188

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.565G>C (p.E189Q) alteration is located in exon 3 (coding exon 3) of the NGFR gene. This alteration results from a G to C substitution at nucleotide position 565, causing the glutamic acid (E) at amino acid position 189 to be replaced by a glutamine (Q). 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

0.094

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.65

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.2

L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.17

Sift

Benign

0.39

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0020

B;.

Vest4

0.22

MutPred

0.27

Gain of MoRF binding (P = 0.0786);.;

MVP

0.75

MPC

0.52

ClinPred

0.63

GERP RS

4.8

Varity_R

0.077

gMVP

0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over