1-156669438-C-T

Variant names:

• chr1-156669438-C-T
• rs1679650326
• NM_006617.2:c.4750G>A

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.4750G>A​(p.Gly1584Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NES NM_006617.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.386
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084082514).

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.4750G>A	p.Gly1584Arg	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.4750G>A	p.Gly1584Arg	missense	Exon 4 of 4	ENSP00000357206.3	P48681
	NES	ENST00000867897.1		c.3784G>A	p.Gly1262Arg	missense	Exon 4 of 4	ENSP00000537956.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461654 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.15
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.39
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.10
Sift	Benign	0.13	T
Sift4G	Benign	0.15	T
Polyphen		0.025	B
Vest4		0.18
MutPred		0.12		Gain of MoRF binding (P = 0.0823)
MVP		0.75
MPC		0.12
ClinPred		0.14	T
GERP RS		2.0
Varity_R		0.056
gMVP		0.010
Mutation Taster		=83/17	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: rs1679650326; hg19: chr1-156639230;