Variant 17-49506500-C-G 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.410C>G(p.Ser137Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NGFR
NM_002507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

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.410C>G	p.Ser137Cys	missense_variant	3/6	ENST00000172229.8
NGFR-AS1	NR_103773.1 linkuse as main transcript	n.378G>C		splice_region_variant, non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8 linkuse as main transcript	c.410C>G	p.Ser137Cys	missense_variant	3/6	1	NM_002507.4	P1	P08138-1
NGFR-AS1	ENST00000514506.1 linkuse as main transcript	n.378G>C		splice_region_variant, non_coding_transcript_exon_variant	3/3	2
NGFR	ENST00000504201.1 linkuse as main transcript	c.128C>G	p.Ser43Cys	missense_variant	3/6	2			P08138-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239460

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131212

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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 12, 2021

The c.410C>G (p.S137C) alteration is located in exon 3 (coding exon 3) of the NGFR gene. This alteration results from a C to G substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 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

0.52

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.12

Cadd

Pathogenic

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.71

D;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Pathogenic

0.84

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.44

Sift

Benign

0.18

T;T

Sift4G

Benign

0.20

T;T

Polyphen

1.0

D;.

Vest4

0.45

MutPred

0.53

Loss of ubiquitination at K141 (P = 0.0531);.;

MVP

0.96

MPC

1.4

ClinPred

0.40

GERP RS

5.4

Varity_R

0.16

gMVP

0.87

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