NES p.Pro1275Arg

Variant names:

• chr1-156670364-G-C
• rs3748570
• NM_006617.2:c.3824C>G
• NES p.Pro1275Arg

Your query was ambiguous. Multiple possible variants found:

• chr1-156670364-G-C
• chr1-156670363-GG-AC
• chr1-156670363-GG-TC
• chr1-156670363-GG-CC
• chr1-156670363-GGG-TCT
• chr1-156670363-GGG-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006617.2(NES):​c.3824C>G​(p.Pro1275Arg) 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. 14/22 in silico tools predict a benign 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. P1275L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NES NM_006617.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 41 publications found

Genes affected

NES (HGNC:7756): (nestin) This gene encodes a member of the intermediate filament protein family and is expressed primarily in nerve cells. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09760898).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006617.2. 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
	NES	NM_006617.2	MANE Select	c.3824C>G	p.Pro1275Arg	missense	Exon 4 of 4	NP_006608.1	P48681

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NES	ENST00000368223.4	TSL:1 MANE Select	c.3824C>G	p.Pro1275Arg	missense	Exon 4 of 4	ENSP00000357206.3	P48681
	NES	ENST00000867897.1		c.2858C>G	p.Pro953Arg	missense	Exon 4 of 4	ENSP00000537956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.2
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.31	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.14	T
Varity_R		0.074
gMVP		0.055
Mutation Taster		=100/0	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

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

Other links and lift over

dbSNP: rs3748570;

hg19: chr1-156640156;