12-5494803-G-T

Variant names:

• chr12-5494803-G-T
• rs1368913522
• NM_001102654.2:c.628G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001102654.2(NTF3):​c.628G>T​(p.Glu210*) variant causes a stop gained change. 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: NTF3 NM_001102654.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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
NTF3	NM_001102654.2	c.628G>T	p.Glu210*	stop_gained	Exon 2 of 2	ENST00000423158.4	NP_001096124.1
NTF3	NM_002527.5	c.589G>T	p.Glu197*	stop_gained	Exon 1 of 1		NP_002518.1
NTF3	XM_011520963.3	c.589G>T	p.Glu197*	stop_gained	Exon 2 of 2		XP_011519265.1
NTF3	XM_047428901.1	c.589G>T	p.Glu197*	stop_gained	Exon 2 of 2		XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000423158.4	c.628G>T	p.Glu210*	stop_gained	Exon 2 of 2	1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000331010.7	c.589G>T	p.Glu197*	stop_gained	Exon 1 of 1	6		ENSP00000328738.6
NTF3	ENST00000535299.5	n.232-11762G>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	47
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		4.2
Vest4		0.80
GERP RS		5.5
Mutation Taster		=2/198	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1368913522; hg19: chr12-5603969;