17-49502067-C-T

Variant names:

• chr17-49502067-C-T
• rs1387942785
• NM_002507.4:c.71C>T

Variant summary

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

The NM_002507.4(NGFR):​c.71C>T​(p.Ser24Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S24Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NGFR NM_002507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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

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 rank	MANE	Protein	UniProt
NGFR	NM_002507.4	c.71C>T	p.Ser24Phe	missense_variant	Exon 2 of 6	ENST00000172229.8	NP_002498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGFR	ENST00000172229.8	c.71C>T	p.Ser24Phe	missense_variant	Exon 2 of 6	1	NM_002507.4	ENSP00000172229.3
NGFR	ENST00000504201	c.-212C>T		5_prime_UTR_variant	Exon 2 of 6	2		ENSP00000421731.1
NGFR	ENST00000509200.5	c.-212C>T		5_prime_UTR_variant	Exon 2 of 3	4		ENSP00000421514.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1192550 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 586808

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.039
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.041	D
Polyphen		0.38	B
Vest4		0.40
MutPred		0.51		Loss of disorder (P = 0.0492);
MVP		0.82
MPC		0.84
ClinPred		0.61	D
GERP RS		4.4
Varity_R		0.12
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs1387942785; hg19: chr17-47579429;