12-5494815-G-A

Position:

• chr12-5494815-G-A

Variant summary

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

The NM_001102654.2(NTF3):​c.640G>A​(p.Val214Ile) variant causes a missense change. 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: 32)
• Consequence: NTF3 NM_001102654.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

Genes affected

NTF3 (HGNC:8023): (neurotrophin 3) The protein encoded by this gene is a member of the neurotrophin family, that controls survival and differentiation of mammalian neurons. This protein is closely related to both nerve growth factor and brain-derived neurotrophic factor. It may be involved in the maintenance of the adult nervous system, and may affect development of neurons in the embryo when it is expressed in human placenta. NTF3-deficient mice generated by gene targeting display severe movement defects of the limbs. The mature peptide of this protein is identical in all mammals examined including human, pig, rat and mouse. [provided by RefSeq, Jul 2008]

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=0.25699925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTF3	NM_001102654.2	c.640G>A	p.Val214Ile	missense_variant	2/2	ENST00000423158.4
NTF3	NM_002527.5	c.601G>A	p.Val201Ile	missense_variant	1/1
NTF3	XM_011520963.3	c.601G>A	p.Val201Ile	missense_variant	2/2
NTF3	XM_047428901.1	c.601G>A	p.Val201Ile	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTF3	ENST00000423158.4	c.640G>A	p.Val214Ile	missense_variant	2/2	1	NM_001102654.2	P4
NTF3	ENST00000331010.7	c.601G>A	p.Val201Ile	missense_variant	1/1			A1
NTF3	ENST00000535299.5	n.232-11750G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jun 16, 2024

The c.601G>A (p.V201I) alteration is located in exon 1 (coding exon 1) of the NTF3 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the valine (V) at amino acid position 201 to be replaced by an isoleucine (I). 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	0.11
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.4	.;L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.021	D;D
Sift4G	Benign	0.074	T;T
Polyphen		0.20	.;B
Vest4		0.27
MutPred		0.49		.;Loss of ubiquitination at K202 (P = 0.0428);
MVP		0.45
MPC		1.5
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-5603981;