Variant 3-115663809-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000393780.3(GAP43):c.31C>T(p.Pro11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,551,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GAP43
ENST00000393780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.160

Variant links:

Genes affected

GAP43 (HGNC:4140): (growth associated protein 43) The protein encoded by this gene has been termed a 'growth' or 'plasticity' protein because it is expressed at high levels in neuronal growth cones during development and axonal regeneration. This protein is considered a crucial component of an effective regenerative response in the nervous system. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GAP43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055648).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAP43	NM_002045.4 linkuse as main transcript	c.31-12204C>T		intron_variant		ENST00000305124.11
GAP43	NM_001130064.2 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAP43	ENST00000393780.3 linkuse as main transcript	c.31C>T	p.Pro11Ser	missense_variant	2/4	1			P17677-2
GAP43	ENST00000305124.11 linkuse as main transcript	c.31-12204C>T		intron_variant		1	NM_002045.4	P1	P17677-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

157198

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000136

AC:

AN:

1399464

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

690236

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:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000139

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.000119

AC:

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

Jul 15, 2021

The c.31C>T (p.P11S) alteration is located in exon 2 (coding exon 1) of the GAP43 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the proline (P) at amino acid position 11 to be replaced by a serine (S). 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

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.78

DANN

Benign

0.94

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.40

M_CAP

Benign

0.0090

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.28

REVEL

Benign

0.0070

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.12

MVP

0.43

MPC

0.17

ClinPred

0.42

GERP RS

1.4

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over