dbSNP rs767323181: ASTN1:p.Val1148Leu (chr1-176876558-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_004319.3(ASTN1):c.3442G>T(p.Val1148Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V1148M) has been classified as Uncertain significance.

Frequency

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

Consequence

ASTN1
NM_004319.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.87

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3 link	c.3442G>T	p.Val1148Leu	missense_variant	Exon 21 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.3442G>T	p.Val1148Leu	missense_variant	Exon 21 of 23	1	NM_004319.3	ENSP00000354536.2	O14525-2
ASTN1	ENST00000367657.7 link	c.3442G>T	p.Val1148Leu	missense_variant	Exon 21 of 23	1		ENSP00000356629.3	B1AJS1
ASTN1	ENST00000424564.2 link	c.3442G>T	p.Val1148Leu	missense_variant	Exon 21 of 22	1		ENSP00000395041.2	O14525-3
ASTN1	ENST00000850957.1 link	c.3466G>T	p.Val1156Leu	missense_variant	Exon 21 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.028

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-1.0

PhyloP100

7.9

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.011

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.81

MutPred

0.21

Loss of methylation at K1152 (P = 0.0786);Loss of methylation at K1152 (P = 0.0786);Loss of methylation at K1152 (P = 0.0786);

MVP

0.31

MPC

0.78

ClinPred

0.94

GERP RS

5.3

gMVP

0.76

Mutation Taster

=36/64

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over