12-5488215-T-C

Variant names:

• chr12-5488215-T-C
• rs4930767
• NM_001102654.2:c.19-5979T>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.19-5979T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,964 control chromosomes in the GnomAD database, including 17,743 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 0.48 (17743 hom., cov: 32)
• Consequence: NTF3 NM_001102654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102654.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF3	NM_001102654.2	MANE Select	c.19-5979T>C		intron	N/A	NP_001096124.1	P20783-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF3	ENST00000423158.4	TSL:1 MANE Select	c.19-5979T>C		intron	N/A	ENSP00000397297.2	P20783-2
	NTF3	ENST00000535299.5	TSL:5	n.232-18350T>C		intron	N/A
	NTF3	ENST00000543548.1	TSL:3	n.209-5979T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72999 AN: 151846 Hom.: 17716 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.481 AC: 73075 AN: 151964 Hom.: 17743 Cov.: 32 AF XY: 0.481 AC XY: 35703 AN XY: 74266

African (AFR) AF: 0.460 AC: 19050 AN: 41430

American (AMR) AF: 0.402 AC: 6146 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1620 AN: 3464

East Asian (EAS) AF: 0.338 AC: 1747 AN: 5162

South Asian (SAS) AF: 0.566 AC: 2730 AN: 4820

European-Finnish (FIN) AF: 0.522 AC: 5516 AN: 10558

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34791 AN: 67954

Other (OTH) AF: 0.459 AC: 965 AN: 2102

Alfa AF: 0.504 Hom.: 10965

Bravo AF: 0.464

Asia WGS AF: 0.494 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	10
DANN	Benign	0.36
PhyloP100		1.1
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: rs4930767; hg19: chr12-5597381;