chr17-49510471-C-T

Position:

• chr17-49510471-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002507.4(NGFR):​c.628C>T​(p.Pro210Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0970

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

ACMG classification

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=0.09555173).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGFR	NM_002507.4	c.628C>T	p.Pro210Ser	missense_variant	4/6	ENST00000172229.8	NP_002498.1
NGFR-AS1	NR_103773.1	n.377+512G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGFR	ENST00000172229.8	c.628C>T	p.Pro210Ser	missense_variant	4/6	1	NM_002507.4	ENSP00000172229.3
NGFR	ENST00000504201.1	c.346C>T	p.Pro116Ser	missense_variant	4/6	2		ENSP00000421731.1
NGFR-AS1	ENST00000514506.1	n.377+512G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 15, 2023

The c.628C>T (p.P210S) alteration is located in exon 4 (coding exon 4) of the NGFR gene. This alteration results from a C to T substitution at nucleotide position 628, causing the proline (P) at amino acid position 210 to be replaced by a serine (S). 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	0.066
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.27	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.030	N;N
REVEL	Benign	0.16
Sift	Benign	0.17	T;D
Sift4G	Benign	0.10	T;T
Polyphen		0.17	B;.
Vest4		0.19
MutPred		0.17		Gain of phosphorylation at P210 (P = 0.0115);.;
MVP		0.61
MPC		0.55
ClinPred		0.061	T
GERP RS		2.8
Varity_R		0.019
gMVP		0.65

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: chr17-47587833;