17-49506418-G-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.328G>T(p.Ala110Ser) 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. 14/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56

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=0.2496944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NGFR	NM_002507.4	c.328G>T	p.Ala110Ser	missense_variant	3/6	ENST00000172229.8
NGFR-AS1	NR_103773.1	n.460C>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NGFR	ENST00000172229.8	c.328G>T	p.Ala110Ser	missense_variant	3/6	1	NM_002507.4	P1
NGFR-AS1	ENST00000514506.1	n.460C>A		non_coding_transcript_exon_variant	3/3	2
NGFR	ENST00000504201.1	c.46G>T	p.Ala16Ser	missense_variant	3/6	2
NGFR	ENST00000509200.5			downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1453704 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723376

Gnomad4 AFR exome AF: 0.00

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 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

Nov 10, 2022

The c.328G>T (p.A110S) alteration is located in exon 3 (coding exon 3) of the NGFR gene. This alteration results from a G to T substitution at nucleotide position 328, causing the alanine (A) at amino acid position 110 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	0.096
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	20
Dann	Benign	0.95
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	0.95	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.20
Sift	Benign	0.84	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0010	B;.
Vest4		0.33
MutPred		0.55		Gain of disorder (P = 0.0587);.;
MVP		0.84
MPC		0.50
ClinPred		0.59	D
GERP RS		3.5
Varity_R		0.044
gMVP		0.55

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: chr17-47583780;