12-5495458-T-C

Variant names:

• chr12-5495458-T-C
• rs6489630
• ENST00000535299.5:n.232-11107T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000535299.5(NTF3):​n.232-11107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,154 control chromosomes in the GnomAD database, including 44,435 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44435 hom., cov: 33)
• Consequence: NTF3 ENST00000535299.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• Publications: 14 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.*470T>C		downstream_gene_variant		ENST00000423158.4	NP_001096124.1
NTF3	NM_002527.5	c.*470T>C		downstream_gene_variant			NP_002518.1
NTF3	XM_011520963.3	c.*470T>C		downstream_gene_variant			XP_011519265.1
NTF3	XM_047428901.1	c.*470T>C		downstream_gene_variant			XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000535299.5	n.232-11107T>C		intron_variant	Intron 1 of 4	5
NTF3	ENST00000423158.4	c.*470T>C		downstream_gene_variant		1	NM_001102654.2	ENSP00000397297.2

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115223 AN: 152036 Hom.: 44409 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.781

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.758 AC: 115306 AN: 152154 Hom.: 44435 Cov.: 33 AF XY: 0.757 AC XY: 56316 AN XY: 74370

African (AFR) AF: 0.604 AC: 25069 AN: 41478

American (AMR) AF: 0.854 AC: 13058 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.884 AC: 3066 AN: 3468

East Asian (EAS) AF: 0.711 AC: 3677 AN: 5174

South Asian (SAS) AF: 0.816 AC: 3935 AN: 4822

European-Finnish (FIN) AF: 0.747 AC: 7912 AN: 10586

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55876 AN: 68008

Other (OTH) AF: 0.779 AC: 1648 AN: 2116

Alfa AF: 0.801 Hom.: 38110

Bravo AF: 0.759

Asia WGS AF: 0.742 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.068
DANN	Benign	0.27
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs6489630; hg19: chr12-5604624;