Variant chr11-124745506-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006176.3(NRGN):c.19A>C(p.Asn7His) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,429,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 0.0000014 ( 0 hom. )

Consequence

NRGN
NM_006176.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

Variant links:

Genes affected

NRGN (HGNC:8000): (neurogranin) Neurogranin (NRGN) is the human homolog of the neuron-specific rat RC3/neurogranin gene. This gene encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. The NRGN gene contains four exons and three introns. The exons 1 and 2 encode the protein and exons 3 and 4 contain untranslated sequences. It is suggested that the NRGN is a direct target for thyroid hormone in human brain, and that control of expression of this gene could underlay many of the consequences of hypothyroidism on mental states during development as well as in adult subjects. [provided by RefSeq, Jul 2008]

NRGN links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.108811796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRGN	NM_006176.3 linkuse as main transcript	c.19A>C	p.Asn7His	missense_variant	2/4	ENST00000284292.11	NP_006167.1
NRGN	NM_001126181.2 linkuse as main transcript	c.19A>C	p.Asn7His	missense_variant	2/4		NP_001119653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NRGN	ENST00000284292.11 linkuse as main transcript	c.19A>C	p.Asn7His	missense_variant	2/4	1	NM_006176.3	ENSP00000284292	P1
NRGN	ENST00000412681.2 linkuse as main transcript	c.19A>C	p.Asn7His	missense_variant	2/4	1		ENSP00000399591	P1
	ENST00000531241.1 linkuse as main transcript	n.183+409T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1429224

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

709666

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:

0.0000241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 28, 2023

The c.19A>C (p.N7H) alteration is located in exon 2 (coding exon 2) of the NRGN gene. This alteration results from a A to C substitution at nucleotide position 19, causing the asparagine (N) at amino acid position 7 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.018

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.66

.;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.097

Sift

Benign

0.19

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.042

B;B

Vest4

0.19

MutPred

0.13

Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);

MVP

0.068

MPC

1.6

ClinPred

0.97

GERP RS

5.6

Varity_R

0.090

gMVP

0.30

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