chr1-71776201-G-C

Position:

• chr1-71776201-G-C

Variant summary

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

The NM_173808.3(NEGR1):​c.506C>G​(p.Ser169Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NEGR1 NM_173808.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90

Genes affected

NEGR1 (HGNC:17302): (neuronal growth regulator 1) Predicted to act upstream of or within several processes, including feeding behavior; locomotory behavior; and positive regulation of neuron projection development. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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	UniProt
NEGR1	NM_173808.3	c.506C>G	p.Ser169Cys	missense_variant	3/7	ENST00000357731.10
NEGR1	XM_011541200.4	c.506C>G	p.Ser169Cys	missense_variant	3/7
NEGR1	XM_011541201.4	c.506C>G	p.Ser169Cys	missense_variant	3/5
NEGR1	XM_017000961.3	c.506C>G	p.Ser169Cys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEGR1	ENST00000357731.10	c.506C>G	p.Ser169Cys	missense_variant	3/7	1	NM_173808.3	P1
NEGR1	ENST00000306821.3	c.122C>G	p.Ser41Cys	missense_variant	3/7	1
NEGR1	ENST00000467479.1	n.503C>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.506C>G (p.S169C) alteration is located in exon 3 (coding exon 3) of the NEGR1 gene. This alteration results from a C to G substitution at nucleotide position 506, causing the serine (S) at amino acid position 169 to be replaced by a cysteine (C). 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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Uncertain	-0.041	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.87	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.051	T;D
Polyphen		0.86	P;.
Vest4		0.54
MutPred		0.51		Loss of disorder (P = 5e-04);.;
MVP		0.52
MPC		1.1
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr1-72241884;