1-156669972-C-T

Variant names:

• chr1-156669972-C-T
• rs760327284
• NM_006617.2:c.4216G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006617.2(NES):​c.4216G>A​(p.Asp1406Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1406G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NES NM_006617.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3069126).

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.4216G>A	p.Asp1406Asn	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.4216G>A	p.Asp1406Asn	missense	Exon 4 of 4	ENSP00000357206.3	P48681
	NES	ENST00000867897.1		c.3250G>A	p.Asp1084Asn	missense	Exon 4 of 4	ENSP00000537956.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 80

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.081
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.085	D
MutationAssessor	Benign	1.9	L
PhyloP100		2.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.27
Sift	Uncertain	0.013	D
Sift4G	Benign	0.075	T
Polyphen		0.99	D
Vest4		0.19
MutPred		0.072		Loss of phosphorylation at S1409 (P = 0.1563)
MVP		0.89
MPC		0.31
ClinPred		0.90	D
GERP RS		4.1
Varity_R		0.13
gMVP		0.022
Mutation Taster		=89/11	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

Other links and lift over

dbSNP: rs760327284; hg19: chr1-156639764;