chr17-49502079-C-A

Variant names:

• chr17-49502079-C-A
• NM_002507.4:c.83C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002507.4(NGFR):​c.83C>A​(p.Ala28Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2479068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	NM_002507.4	MANE Select	c.83C>A	p.Ala28Asp	missense	Exon 2 of 6	NP_002498.1	P08138-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGFR	ENST00000172229.8	TSL:1 MANE Select	c.83C>A	p.Ala28Asp	missense	Exon 2 of 6	ENSP00000172229.3	P08138-1
	NGFR	ENST00000504201.1	TSL:2	c.-200C>A		5_prime_UTR	Exon 2 of 6	ENSP00000421731.1	P08138-2
	NGFR	ENST00000509200.5	TSL:4	c.-200C>A		5_prime_UTR	Exon 2 of 3	ENSP00000421514.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.26
Sift	Benign	0.044	D
Sift4G	Benign	0.14	T
Polyphen		0.026	B
Vest4		0.31
MutPred		0.43		Loss of ubiquitination at K29 (P = 0.0937)
MVP		0.91
MPC		0.85
ClinPred		0.45	T
GERP RS		4.2
Varity_R		0.21
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr17-47579441;