12-5432458-C-G

Variant names:

• chr12-5432458-C-G
• rs71578945
• NM_001102654.2:c.18+116C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001102654.2(NTF3):​c.18+116C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,142,298 control chromosomes in the GnomAD database, including 96 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 0.0084 (13 hom., cov: 29)
  • Exomes 𝑓: 0.011 (83 hom.)
• Consequence: NTF3 NM_001102654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BS2: High AC in GnomAd4 at 1276 AD gene.

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.18+116C>G		intron	N/A	NP_001096124.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF3	ENST00000423158.4	TSL:1 MANE Select	c.18+116C>G		intron	N/A	ENSP00000397297.2
	NTF3	ENST00000535299.5	TSL:5	n.231+116C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00841 AC: 1276 AN: 151812 Hom.: 13 Cov.: 29

Gnomad AFR AF: 0.00230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00505

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00336

GnomAD4 exome AF: 0.0114 AC: 11246 AN: 990368 Hom.: 83 AF XY: 0.0113 AC XY: 5681 AN XY: 501436

African (AFR) AF: 0.00195 AC: 48 AN: 24646

American (AMR) AF: 0.00406 AC: 148 AN: 36466

Ashkenazi Jewish (ASJ) AF: 0.00143 AC: 29 AN: 20320

East Asian (EAS) AF: 0.00 AC: 0 AN: 36156

South Asian (SAS) AF: 0.00602 AC: 413 AN: 68580

European-Finnish (FIN) AF: 0.0228 AC: 797 AN: 34904

Middle Eastern (MID) AF: 0.00701 AC: 25 AN: 3564

European-Non Finnish (NFE) AF: 0.0130 AC: 9343 AN: 721162

Other (OTH) AF: 0.00994 AC: 443 AN: 44570

GnomAD4 genome AF: 0.00840 AC: 1276 AN: 151930 Hom.: 13 Cov.: 29 AF XY: 0.00848 AC XY: 630 AN XY: 74262

African (AFR) AF: 0.00229 AC: 95 AN: 41440

American (AMR) AF: 0.00511 AC: 78 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00333 AC: 16 AN: 4800

European-Finnish (FIN) AF: 0.0236 AC: 250 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0122 AC: 827 AN: 67960

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.0101 Hom.: 1

Bravo AF: 0.00718

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		1.1
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71578945; hg19: chr12-5541624;