rs1017274820

Variant names:

• chr19-49061841-G-A
• rs1017274820
• NM_006179.5:c.157C>T

Variant summary

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

The NM_006179.5(NTF4):​c.157C>T​(p.Pro53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,398,420 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: NTF4 NM_006179.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.798
• Publications: 0 publications found

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]

NTF4 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, O

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000283663 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22986528).
• BS2: High AC in GnomAdExome4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006179.5. 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
	NTF4	NM_006179.5	MANE Select	c.157C>T	p.Pro53Ser	missense	Exon 2 of 2	NP_006170.1	P34130
	NTF4	NM_001395489.1		c.157C>T	p.Pro53Ser	missense	Exon 3 of 3	NP_001382418.1	P34130

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTF4	ENST00000593537.2	TSL:6 MANE Select	c.157C>T	p.Pro53Ser	missense	Exon 2 of 2	ENSP00000469455.1	P34130
	ENSG00000283663	ENST00000599795.5	TSL:2	n.157C>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000470689.1	M0QZQ0
	NTF4	ENST00000594938.2	TSL:5	c.157C>T	p.Pro53Ser	missense	Exon 3 of 3	ENSP00000512387.1	P34130

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000134 AC: 2 AN: 148966 AF XY: 0.0000251

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 22 AN: 1398420 Hom.: 0 Cov.: 32 AF XY: 0.0000188 AC XY: 13 AN XY: 689878

African (AFR) AF: 0.00 AC: 0 AN: 31610

American (AMR) AF: 0.00 AC: 0 AN: 35724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 35742

South Asian (SAS) AF: 0.00 AC: 0 AN: 79350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.0000204 AC: 22 AN: 1079112

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.80
PrimateAI	Uncertain	0.61	T
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.25
MutPred		0.34		Gain of phosphorylation at P53 (P = 0.0233)
MVP		0.77
ClinPred		0.27	T
GERP RS		2.6
PromoterAI		-0.012	Neutral
Varity_R		0.18
gMVP		0.68
Mutation Taster		=275/25	polymorphism

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

Other links and lift over

dbSNP: rs1017274820; hg19: chr19-49565098;