chr6-11190358-T-C

Position:

chr6-11190358-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006403.4(NEDD9):c.1511A>G(p.His504Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000171 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

NEDD9
NM_006403.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.78

Variant links:

Genes affected

NEDD9 (HGNC:7733): (neural precursor cell expressed, developmentally down-regulated 9) The protein encoded by this gene is a member of the CRK-associated substrates family. Members of this family are adhesion docking molecules that mediate protein-protein interactions for signal transduction pathways. This protein is a focal adhesion protein that acts as a scaffold to regulate signaling complexes important in cell attachment, migration and invasion as well as apoptosis and the cell cycle. This protein has also been reported to have a role in cancer metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

NEDD9 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005346447).

BP6

Variant 6-11190358-T-C is Benign according to our data. Variant chr6-11190358-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 727676.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NEDD9	NM_006403.4 linkuse as main transcript	c.1511A>G	p.His504Arg	missense_variant	5/7	ENST00000379446.10
NEDD9	NM_001142393.2 linkuse as main transcript	c.1511A>G	p.His504Arg	missense_variant	6/8
NEDD9	NM_001271033.2 linkuse as main transcript	c.1064A>G	p.His355Arg	missense_variant	4/6
NEDD9	NR_073131.1 linkuse as main transcript	n.2118A>G		non_coding_transcript_exon_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD9	ENST00000379446.10 linkuse as main transcript	c.1511A>G	p.His504Arg	missense_variant	5/7	1	NM_006403.4	P4	Q14511-1
	ENST00000500636.2 linkuse as main transcript	n.175+5140T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000286

AC:

AN:

251472

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00406

Gnomad AMR exome

AF:

0.0000867

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:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00293

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152318

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00356

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0216

Hom.:

2309

Bravo

AF:

0.00117

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000354

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

NEDD9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 10, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

T;T;.

Eigen

Benign

0.019

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0053

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

M;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.18

N;.;N

REVEL

Benign

0.045

Sift

Benign

0.060

T;.;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.026

B;.;.

Vest4

0.21

MVP

0.43

MPC

0.27

ClinPred

0.016

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.22

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