12-5494441-G-C

Variant names:

• chr12-5494441-G-C
• rs1805149
• NM_001102654.2:c.266G>C

Variant summary

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

The NM_001102654.2(NTF3):​c.266G>C​(p.Gly89Ala) 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. 14/21 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: 31)
• Consequence: NTF3 NM_001102654.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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=0.080054075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.266G>C	p.Gly89Ala	missense_variant	Exon 2 of 2	ENST00000423158.4	NP_001096124.1
NTF3	NM_002527.5	c.227G>C	p.Gly76Ala	missense_variant	Exon 1 of 1		NP_002518.1
NTF3	XM_011520963.3	c.227G>C	p.Gly76Ala	missense_variant	Exon 2 of 2		XP_011519265.1
NTF3	XM_047428901.1	c.227G>C	p.Gly76Ala	missense_variant	Exon 2 of 2		XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000423158.4	c.266G>C	p.Gly89Ala	missense_variant	Exon 2 of 2	1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000331010.7	c.227G>C	p.Gly76Ala	missense_variant	Exon 1 of 1	6		ENSP00000328738.6
NTF3	ENST00000543548.1	n.456G>C		non_coding_transcript_exon_variant	Exon 2 of 2	3
NTF3	ENST00000535299.5	n.232-12124G>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.034
Sift	Benign	0.092	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.0010	.;B
Vest4		0.052
MutPred		0.17		.;Loss of catalytic residue at G76 (P = 0.0413);
MVP		0.19
MPC		0.92
ClinPred		0.18	T
GERP RS		4.8
Varity_R		0.037
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1805149; hg19: chr12-5603607;