rs6332

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-5494466-G-A
• chr12-5494466-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.291G>A	p.Pro97Pro	synonymous_variant	Exon 2 of 2	ENST00000423158.4	NP_001096124.1
NTF3	NM_002527.5	c.252G>A	p.Pro84Pro	synonymous_variant	Exon 1 of 1		NP_002518.1
NTF3	XM_011520963.3	c.252G>A	p.Pro84Pro	synonymous_variant	Exon 2 of 2		XP_011519265.1
NTF3	XM_047428901.1	c.252G>A	p.Pro84Pro	synonymous_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.291G>A	p.Pro97Pro	synonymous_variant	Exon 2 of 2	1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000331010.7	c.252G>A	p.Pro84Pro	synonymous_variant	Exon 1 of 1	6		ENSP00000328738.6
NTF3	ENST00000543548.1	n.481G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3
NTF3	ENST00000535299.5	n.232-12099G>A		intron_variant	Intron 1 of 4	5

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

GnomAD3 exomes AF: 0.485 AC: 121568 AN: 250580 Hom.: 29919 AF XY: 0.489 AC XY: 66301 AN XY: 135550

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 SAS exome AF: 0.493

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

Gnomad4 AFR exome AF: 0.530

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.507

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

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.508

Alfa AF: 0.503 Hom.: 37902

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.15
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs6332; hg19: chr12-5603632; COSMIC: COSV58417372;