6-6006731-C-A

Variant names:

• chr6-6006731-C-A
• rs145415171
• NM_016588.3:c.19G>T

Variant summary

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

The NM_016588.3(NRN1):​c.19G>T​(p.Gly7Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. G7R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRN1 NM_016588.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97
• Publications: 0 publications found

Genes affected

NRN1 (HGNC:17972): (neuritin 1) This gene encodes a member of the neuritin family, and is expressed in postmitotic-differentiating neurons of the developmental nervous system and neuronal structures associated with plasticity in the adult. The expression of this gene can be induced by neural activity and neurotrophins. The encoded protein contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins. The encoded protein promotes neurite outgrowth and arborization, suggesting its role in promoting neuritogenesis. Overexpression of the encoded protein may be associated with astrocytoma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016588.3. 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
	NRN1	NM_016588.3	MANE Select	c.19G>T	p.Gly7Cys	missense	Exon 1 of 3	NP_057672.1	Q9NPD7
	NRN1	NM_001278710.2		c.19G>T	p.Gly7Cys	missense	Exon 2 of 4	NP_001265639.1	Q9NPD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRN1	ENST00000244766.7	TSL:1 MANE Select	c.19G>T	p.Gly7Cys	missense	Exon 1 of 3	ENSP00000244766.2	Q9NPD7
	NRN1	ENST00000616243.1	TSL:4	c.19G>T	p.Gly7Cys	missense	Exon 2 of 4	ENSP00000484055.1	Q9NPD7
	NRN1	ENST00000889857.1		c.19G>T	p.Gly7Cys	missense	Exon 2 of 4	ENSP00000559916.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.46	N
PhyloP100		6.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.18	T
Polyphen		0.54	P
Vest4		0.75
MutPred		0.43		Loss of disorder (P = 0.0077)
MVP		0.21
MPC		0.78
ClinPred		0.77	D
GERP RS		4.1
PromoterAI		-0.029	Neutral
Varity_R		0.41
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs145415171; hg19: chr6-6006964;