NM_006179.5:c.613A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS2_Supporting

The NM_006179.5(NTF4):ā€‹c.613A>Gā€‹(p.Ser205Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

NTF4
NM_006179.5 missense

Scores

5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32
Variant links:
Genes affected
NTF4 (HGNC:8024): (neurotrophin 4) This gene is a member of a family of neurotrophic factors, neurotrophins, that control survival and differentiation of mammalian neurons. The expression of this gene is ubiquitous and less influenced by environmental signals. While knock-outs of other neurotrophins including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 prove lethal during early postnatal development, NTF5-deficient mice only show minor cellular deficits and develop normally to adulthood. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3409763).
BS2
High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTF4NM_006179.5 linkc.613A>G p.Ser205Gly missense_variant Exon 2 of 2 ENST00000593537.2 NP_006170.1 P34130A0A024QZE4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTF4ENST00000593537.2 linkc.613A>G p.Ser205Gly missense_variant Exon 2 of 2 6 NM_006179.5 ENSP00000469455.1 P34130
ENSG00000283663ENST00000599795.5 linkn.243+370A>G intron_variant Intron 3 of 6 2 ENSP00000470689.1 M0QZQ0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250064
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460370
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726524
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jul 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.613A>G (p.S205G) alteration is located in exon 2 (coding exon 1) of the NTF4 gene. This alteration results from a A to G substitution at nucleotide position 613, causing the serine (S) at amino acid position 205 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Benign
0.13
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.59
T
Sift4G
Benign
0.075
T
Polyphen
0.98
D
Vest4
0.14
MutPred
0.59
Loss of glycosylation at S205 (P = 0.0036);
MVP
0.79
ClinPred
0.70
D
GERP RS
3.3
Varity_R
0.32
gMVP
0.56

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1035055452; hg19: chr19-49564642; API