rs1662772068

Variant names:

• chr1-212445915-C-G
• rs1662772068
• NM_013349.5:c.428C>G

Variant summary

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

The NM_013349.5(NENF):​c.428C>G​(p.Thr143Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NENF NM_013349.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

Genes affected

NENF (HGNC:30384): (neudesin neurotrophic factor) This gene encodes a neurotrophic factor that may play a role in neuron differentiation and development. A pseudogene of this gene is found on chromosome 12. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2009]

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
NENF	NM_013349.5	c.428C>G	p.Thr143Ser	missense_variant	Exon 4 of 4	ENST00000366988.5	NP_037481.1
NENF	NR_026598.2	n.391C>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NENF	ENST00000366988.5	c.428C>G	p.Thr143Ser	missense_variant	Exon 4 of 4	1	NM_013349.5	ENSP00000355955.3
NENF	ENST00000473900.1	n.418C>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
NENF	ENST00000479589.5	n.388C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.428C>G (p.T143S) alteration is located in exon 4 (coding exon 4) of the NENF gene. This alteration results from a C to G substitution at nucleotide position 428, causing the threonine (T) at amino acid position 143 to be replaced by a serine (S). 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	Benign	0.34
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.68
Sift	Benign	0.061	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.57		Gain of catalytic residue at T143 (P = 0.012);
MVP		0.90
MPC		0.28
ClinPred		0.97	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.60

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: rs1662772068; hg19: chr1-212619257;