rs797044939

Variant names:

• chr19-49061477-T-C
• rs797044939
• NM_006179.5:c.521A>G
• NTF4 p.Gln174Arg

Your query was ambiguous. Multiple possible variants found:

• chr19-49061477-T-C
• chr19-49061477-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_006179.5(NTF4):​c.521A>G​(p.Gln174Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTF4 NM_006179.5 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.67
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763
• PP5: Variant 19-49061477-T-C is Pathogenic according to our data. Variant chr19-49061477-T-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 208763.Status of the report is criteria_provided_single_submitter, 1 stars.

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.521A>G	p.Gln174Arg	missense	Exon 2 of 2	NP_006170.1	P34130
	NTF4	NM_001395489.1		c.521A>G	p.Gln174Arg	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.521A>G	p.Gln174Arg	missense	Exon 2 of 2	ENSP00000469455.1	P34130
	ENSG00000283663	ENST00000599795.5	TSL:2	n.243+278A>G		intron	N/A	ENSP00000470689.1	M0QZQ0
	NTF4	ENST00000594938.2	TSL:5	c.521A>G	p.Gln174Arg	missense	Exon 3 of 3	ENSP00000512387.1	P34130

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely pathogenic

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	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.7
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.0060	D
Varity_R		0.35
gMVP		0.69
Mutation Taster		=58/42	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs797044939;

hg19: chr19-49564734;