12-5494466-G-A

Variant names:

• chr12-5494466-G-A
• rs6332
• NM_001102654.2:c.291G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001102654.2(NTF3):​c.291G>A​(p.Pro97Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,613,108 control chromosomes in the GnomAD database, including 207,508 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 0.50 (19187 hom., cov: 29)
  • Exomes 𝑓: 0.51 (188321 hom.)
• Consequence: NTF3 NM_001102654.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 42 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-2.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF3	NM_001102654.2	MANE Select	c.291G>A	p.Pro97Pro	synonymous	Exon 2 of 2	NP_001096124.1
	NTF3	NM_002527.5		c.252G>A	p.Pro84Pro	synonymous	Exon 1 of 1	NP_002518.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF3	ENST00000423158.4	TSL:1 MANE Select	c.291G>A	p.Pro97Pro	synonymous	Exon 2 of 2	ENSP00000397297.2
	NTF3	ENST00000331010.7	TSL:6	c.252G>A	p.Pro84Pro	synonymous	Exon 1 of 1	ENSP00000328738.6
	NTF3	ENST00000543548.1	TSL:3	n.481G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75715 AN: 151516 Hom.: 19176 Cov.: 29

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.508

GnomAD2 exomes AF: 0.485 AC: 121568 AN: 250580 AF XY: 0.489

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.473

Gnomad FIN exome AF: 0.435

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.506 AC: 739548 AN: 1461474 Hom.: 188321 Cov.: 82 AF XY: 0.507 AC XY: 368641 AN XY: 727052

African (AFR) AF: 0.530 AC: 17729 AN: 33480

American (AMR) AF: 0.392 AC: 17519 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14806 AN: 26136

East Asian (EAS) AF: 0.448 AC: 17771 AN: 39700

South Asian (SAS) AF: 0.494 AC: 42575 AN: 86258

European-Finnish (FIN) AF: 0.439 AC: 23262 AN: 53016

Middle Eastern (MID) AF: 0.556 AC: 3209 AN: 5768

European-Non Finnish (NFE) AF: 0.514 AC: 572037 AN: 1112002

Other (OTH) AF: 0.507 AC: 30640 AN: 60394

GnomAD4 genome AF: 0.500 AC: 75771 AN: 151634 Hom.: 19187 Cov.: 29 AF XY: 0.497 AC XY: 36782 AN XY: 74052

African (AFR) AF: 0.523 AC: 21637 AN: 41340

American (AMR) AF: 0.443 AC: 6749 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2346 AN: 5110

South Asian (SAS) AF: 0.476 AC: 2259 AN: 4750

European-Finnish (FIN) AF: 0.430 AC: 4519 AN: 10506

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34607 AN: 67912

Other (OTH) AF: 0.508 AC: 1069 AN: 2104

Alfa AF: 0.505 Hom.: 73416

Bravo AF: 0.502

Asia WGS AF: 0.464 AC: 1615 AN: 3478

EpiCase AF: 0.510

EpiControl AF: 0.512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.72
PhyloP100		-2.4
PromoterAI		0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6332; hg19: chr12-5603632; COSMIC: COSV58417372;