19-49061940-C-A

Position:

• chr19-49061940-C-A

Variant summary

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

The NM_006179.5(NTF4):​c.58G>T​(p.Val20Leu) 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. 13/19 in silico tools predict a benign 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.280

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07146707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTF4	NM_006179.5	c.58G>T	p.Val20Leu	missense_variant	2/2	ENST00000593537.2	NP_006170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTF4	ENST00000593537.2	c.58G>T	p.Val20Leu	missense_variant	2/2	6	NM_006179.5	ENSP00000469455.1
ENSG00000283663	ENST00000599795.5	n.58G>T		non_coding_transcript_exon_variant	3/7	2		ENSP00000470689.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.58G>T (p.V20L) alteration is located in exon 2 (coding exon 1) of the NTF4 gene. This alteration results from a G to T substitution at nucleotide position 58, causing the valine (V) at amino acid position 20 to be replaced by a leucine (L). 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	0.088
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.42	T;.
Polyphen		0.0030	B;.
Vest4		0.12
MutPred		0.15		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.44
ClinPred		0.14	T
GERP RS		1.9
Varity_R		0.030
gMVP		0.24

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: chr19-49565197;