NM_006179.5:c.397C>A

Variant names:

• chr19-49061601-G-T
• rs144842220
• NM_006179.5:c.397C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006179.5(NTF4):​c.397C>A​(p.Arg133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R133H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NTF4 NM_006179.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ENSG00000283663 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTF4	NM_006179.5	c.397C>A	p.Arg133Ser	missense_variant	Exon 2 of 2	ENST00000593537.2	NP_006170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTF4	ENST00000593537.2	c.397C>A	p.Arg133Ser	missense_variant	Exon 2 of 2	6	NM_006179.5	ENSP00000469455.1
ENSG00000283663	ENST00000599795.5	n.243+154C>A		intron_variant	Intron 3 of 6	2		ENSP00000470689.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461536 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727078

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;.
Eigen	Benign	0.043
Eigen_PC	Benign	0.030
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.61	T
Sift4G	Uncertain	0.0020	D;.
Polyphen		0.92	P;.
Vest4		0.44
MutPred		0.68		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.75
ClinPred		0.73	D
GERP RS		3.1
Varity_R		0.43
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

Other links and lift over

dbSNP: rs144842220; hg19: chr19-49564858;