rs368519726

Variant names:

• chr1-212444375-C-A
• rs368519726
• NM_013349.5:c.275C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-212444375-C-A
• chr1-212444375-C-G
• chr1-212444375-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013349.5(NENF):​c.275C>A​(p.Thr92Lys) 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. 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. T92M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NENF NM_013349.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.847

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NENF	NM_013349.5	c.275C>A	p.Thr92Lys	missense_variant	Exon 3 of 4	ENST00000366988.5	NP_037481.1
NENF	NR_026598.2	n.238C>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NENF	ENST00000366988.5	c.275C>A	p.Thr92Lys	missense_variant	Exon 3 of 4	1	NM_013349.5	ENSP00000355955.3
NENF	ENST00000473900.1	n.265C>A		non_coding_transcript_exon_variant	Exon 3 of 4	2
NENF	ENST00000479589.5	n.235C>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.066
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.019	D
Polyphen		0.48	P
Vest4		0.71
MutPred		0.75		Gain of methylation at T92 (P = 0.0121);
MVP		0.86
MPC		0.053
ClinPred		0.91	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.23
gMVP		0.68

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: rs368519726; hg19: chr1-212617717;