NM_001102654.2:c.18+19692T>C

Variant names:

• chr12-5452034-T-C
• rs10492095
• NM_001102654.2:c.18+19692T>C

Variant summary

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

The NM_001102654.2(NTF3):​c.18+19692T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,224 control chromosomes in the GnomAD database, including 8,457 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 0.33 (8457 hom., cov: 30)
• Consequence: NTF3 NM_001102654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.18+19692T>C		intron_variant	Intron 1 of 1	ENST00000423158.4	NP_001096124.1
NTF3	XM_011520963.3	c.-22+18702T>C		intron_variant	Intron 1 of 1		XP_011519265.1
NTF3	XM_047428901.1	c.-22+20841T>C		intron_variant	Intron 1 of 1		XP_047284857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF3	ENST00000423158.4	c.18+19692T>C		intron_variant	Intron 1 of 1	1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000535299.5	n.231+19692T>C		intron_variant	Intron 1 of 4	5
NTF3	ENST00000543548.1	n.208+18702T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49619 AN: 151112 Hom.: 8452 Cov.: 30

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.328 AC: 49657 AN: 151224 Hom.: 8457 Cov.: 30 AF XY: 0.332 AC XY: 24537 AN XY: 73830

African (AFR) AF: 0.321 AC: 13224 AN: 41174

American (AMR) AF: 0.427 AC: 6497 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3466

East Asian (EAS) AF: 0.565 AC: 2865 AN: 5068

South Asian (SAS) AF: 0.421 AC: 2019 AN: 4800

European-Finnish (FIN) AF: 0.284 AC: 2937 AN: 10356

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.297 AC: 20151 AN: 67834

Other (OTH) AF: 0.308 AC: 648 AN: 2104

Alfa AF: 0.309 Hom.: 22382

Bravo AF: 0.339

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.69
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10492095; hg19: chr12-5561200;