rs562474394

Variant names:

• chr19-49061372-C-G
• rs562474394
• NM_006179.5:c.626G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49061372-C-G
• chr19-49061372-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006179.5(NTF4):​c.626G>C​(p.Arg209Pro) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTF4 NM_006179.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22

Genes affected

NTF4 (HGNC:8024): (neurotrophin 4) This gene is a member of a family of neurotrophic factors, neurotrophins, that control survival and differentiation of mammalian neurons. The expression of this gene is ubiquitous and less influenced by environmental signals. While knock-outs of other neurotrophins including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 prove lethal during early postnatal development, NTF5-deficient mice only show minor cellular deficits and develop normally to adulthood. [provided by RefSeq, Jul 2008]

ENSG00000283663 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF4	NM_006179.5	c.626G>C	p.Arg209Pro	missense_variant	Exon 2 of 2	ENST00000593537.2	NP_006170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF4	ENST00000593537.2	c.626G>C	p.Arg209Pro	missense_variant	Exon 2 of 2	6	NM_006179.5	ENSP00000469455.1
ENSG00000283663	ENST00000599795.5	n.243+383G>C		intron_variant	Intron 3 of 6	2		ENSP00000470689.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D
Eigen	Benign	0.17
Eigen_PC	Benign	0.053
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.67	T
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.61		Loss of MoRF binding (P = 1e-04);
MVP		0.75
ClinPred		0.94	D
GERP RS		3.3
Varity_R		0.58
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs562474394; hg19: chr19-49564629;