NM_004319.3:c.3283A>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_004319.3(ASTN1):c.3283A>C(p.Met1095Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,614,114 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

ASTN1
NM_004319.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 7.60

Variant links:

Genes affected

ASTN1 (HGNC:773): (astrotactin 1) Astrotactin is a neuronal adhesion molecule required for glial-guided migration of young postmitotic neuroblasts in cortical regions of developing brain, including cerebrum, hippocampus, cerebellum, and olfactory bulb (Fink et al., 1995).[supplied by OMIM, Jun 2009]

ASTN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007880479).

BP6

Variant 1-176882938-T-G is Benign according to our data. Variant chr1-176882938-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 438600.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3 link	c.3283A>C	p.Met1095Leu	missense_variant	Exon 20 of 23	ENST00000361833.7	NP_004310.1	A6H8Y4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASTN1	ENST00000361833.7 link	c.3283A>C	p.Met1095Leu	missense_variant	Exon 20 of 23	1	NM_004319.3	ENSP00000354536.2	O14525-2
ASTN1	ENST00000367657.7 link	c.3283A>C	p.Met1095Leu	missense_variant	Exon 20 of 23	1		ENSP00000356629.3	B1AJS1
ASTN1	ENST00000424564.2 link	c.3283A>C	p.Met1095Leu	missense_variant	Exon 20 of 22	1		ENSP00000395041.2	O14525-3

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00747

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00395

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00348

AC:

876

AN:

251406

Hom.:

AF XY:

0.00381

AC XY:

517

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00741

Gnomad FIN exome

AF:

0.000970

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00380

AC:

5549

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2850

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00976

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00693

Gnomad4 FIN exome

AF:

0.000880

Gnomad4 NFE exome

AF:

0.00389

Gnomad4 OTH exome

AF:

0.00364

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152234

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00748

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00395

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00249

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00342

AC:

415

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00439

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ASTN1: BS2 -

Abnormal corpus callosum morphology

Uncertain:1

Sep 01, 2017

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

this variant was indentified in an individual with malformations of cortical development -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.047

T;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.74

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.088

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.26

B;B;.

Vest4

0.63

MutPred

0.12

Loss of methylation at K1090 (P = 0.0888);Loss of methylation at K1090 (P = 0.0888);Loss of methylation at K1090 (P = 0.0888);

MVP

0.37

MPC

0.55

ClinPred

0.039

GERP RS

5.7

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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