rs71578945

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-5432458-C-A
• chr12-5432458-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001102654.2(NTF3):​c.18+116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 990,432 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: NTF3 NM_001102654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF3	NM_001102654.2	c.18+116C>A		intron_variant	Intron 1 of 1	ENST00000423158.4	NP_001096124.1
NTF3	XM_047428901.1	c.-22+1265C>A		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+116C>A		intron_variant	Intron 1 of 1	1	NM_001102654.2	ENSP00000397297.2
NTF3	ENST00000535299.5	n.231+116C>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 990432 Hom.: 0 AF XY: 0.00000199 AC XY: 1 AN XY: 501462

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24646

American (AMR) AF: 0.00 AC: 0 AN: 36466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20320

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 68582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3564

European-Non Finnish (NFE) AF: 0.00000139 AC: 1 AN: 721224

Other (OTH) AF: 0.00 AC: 0 AN: 44570

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.92
PhyloP100		1.1
PromoterAI		-0.15	Neutral

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;