chr4-121036509-T-C

Position:

• chr4-121036509-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024574.4(NDNF):​c.1462A>G​(p.Asn488Asp) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NDNF NM_024574.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

NDNF (HGNC:26256): (neuron derived neurotrophic factor) Predicted to enable heparin binding activity. Involved in several processes, including cellular response to hypoxia; negative regulation of apoptotic process; and nitric oxide mediated signal transduction. Located in extracellular space. Implicated in hypogonadotropic hypogonadism. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031437725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDNF	NM_024574.4	c.1462A>G	p.Asn488Asp	missense_variant	4/4	ENST00000379692.9
NDNF	XM_024454212.2	c.1462A>G	p.Asn488Asp	missense_variant	4/4
NDNF	XM_024454213.2	c.1462A>G	p.Asn488Asp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDNF	ENST00000379692.9	c.1462A>G	p.Asn488Asp	missense_variant	4/4	1	NM_024574.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.94
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.63	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.38	T
Sift4G	Benign	0.33	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.46		Gain of helix (P = 0.062);
MVP		0.14
MPC		0.13
ClinPred		0.093	T
GERP RS		-0.73
Varity_R		0.080
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-121957664;