Variant chr1-156669926-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000368223.4(NES):c.4262A>G(p.Glu1421Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,401,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NES
ENST00000368223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

Variant links:

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]

NES links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
NES	NM_006617.2 linkuse as main transcript	c.4262A>G	p.Glu1421Gly	missense_variant	4/4	ENST00000368223.4	NP_006608.1	P48681Q9H6U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NES	ENST00000368223.4 linkuse as main transcript	c.4262A>G	p.Glu1421Gly	missense_variant	4/4	1	NM_006617.2	ENSP00000357206.3		P48681

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137438

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1401190

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

697460

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000281

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000728

AC:

AN:

137438

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66512

show subpopulations

Gnomad4 AFR

AF:

0.0000278

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.4262A>G (p.E1421G) alteration is located in exon 4 (coding exon 4) of the NES gene. This alteration results from a A to G substitution at nucleotide position 4262, causing the glutamic acid (E) at amino acid position 1421 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.24

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.73

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.27

Sift

Benign

0.10

Sift4G

Uncertain

0.040

Polyphen

1.0

Vest4

0.20

MutPred

0.058

Gain of glycosylation at S1418 (P = 0.0957);

MVP

0.91

MPC

0.38

ClinPred

0.93

GERP RS

4.8

Varity_R

0.22

gMVP

0.019

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over