Variant 17-49506634-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002507.4(NGFR):c.544C>T(p.Arg182Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,380,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

NGFR
NM_002507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt
NGFR	NM_002507.4 linkuse as main transcript	c.544C>T	p.Arg182Cys	missense_variant	3/6	ENST00000172229.8
NGFR-AS1	NR_103773.1 linkuse as main transcript	n.378-134G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8 linkuse as main transcript	c.544C>T	p.Arg182Cys	missense_variant	3/6	1	NM_002507.4	P1	P08138-1
NGFR-AS1	ENST00000514506.1 linkuse as main transcript	n.378-134G>A		intron_variant, non_coding_transcript_variant		2
NGFR	ENST00000504201.1 linkuse as main transcript	c.262C>T	p.Arg88Cys	missense_variant	3/6	2			P08138-2

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

141566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000242

AC:

AN:

1238650

Hom.:

Cov.:

AF XY:

0.00000328

AC XY:

AN XY:

609498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000277

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:

0.00000206

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000141

AC:

AN:

141566

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68290

show subpopulations

Gnomad4 AFR

AF:

0.0000262

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000854

AC:

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.544C>T (p.R182C) alteration is located in exon 3 (coding exon 3) of the NGFR gene. This alteration results from a C to T substitution at nucleotide position 544, causing the arginine (R) at amino acid position 182 to be replaced by a cysteine (C). 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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.65

D;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

0.63

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.96

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.3

N;N

REVEL

Uncertain

0.62

Sift

Benign

0.040

D;D

Sift4G

Benign

0.077

T;T

Polyphen

0.92

P;.

Vest4

0.50

MutPred

0.58

Gain of catalytic residue at W183 (P = 6e-04);.;

MVP

0.90

MPC

1.4

ClinPred

0.83

GERP RS

4.8

Varity_R

0.14

gMVP

0.75

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