17-49506568-C-T

Position:

• chr17-49506568-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.478C>T​(p.His160Tyr) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17

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=0.22428623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGFR	NM_002507.4	c.478C>T	p.His160Tyr	missense_variant	3/6	ENST00000172229.8	NP_002498.1
NGFR-AS1	NR_103773.1	n.378-68G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGFR	ENST00000172229.8	c.478C>T	p.His160Tyr	missense_variant	3/6	1	NM_002507.4	ENSP00000172229.3
NGFR	ENST00000504201.1	c.196C>T	p.His66Tyr	missense_variant	3/6	2		ENSP00000421731.1
NGFR-AS1	ENST00000514506.1	n.378-68G>A		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Jul 02, 2024

The c.478C>T (p.H160Y) 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 478, causing the histidine (H) at amino acid position 160 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T;.
Eigen	Benign	-0.099
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.99	L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.34
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.59	P;.
Vest4		0.45
MutPred		0.52		Gain of phosphorylation at H160 (P = 0.0378);.;
MVP		0.87
MPC		0.64
ClinPred		0.58	D
GERP RS		5.3
Varity_R		0.078
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-47583930;