NM_004319.3:c.3878A>G

Variant names:

• chr1-176864291-T-C
• rs61756323
• NM_004319.3:c.3878A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004319.3(ASTN1):​c.3878A>G​(p.Glu1293Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00333 in 1,613,990 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (21 hom.)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.30
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033033192).
• BP6: Variant 1-176864291-T-C is Benign according to our data. Variant chr1-176864291-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2639585.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.3878A>G	p.Glu1293Gly	missense_variant	Exon 23 of 23	ENST00000361833.7	NP_004310.1
ASTN1	NM_001364856.2	c.3902A>G	p.Glu1301Gly	missense_variant	Exon 23 of 23		NP_001351785.1
ASTN1	NM_001286164.2	c.3647+4553A>G		intron_variant	Intron 22 of 22		NP_001273093.1
ASTN1	XM_017001341.3	c.3671+4553A>G		intron_variant	Intron 22 of 22		XP_016856830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.3878A>G	p.Glu1293Gly	missense_variant	Exon 23 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3647+4553A>G		intron_variant	Intron 22 of 22	1		ENSP00000356629.3
ASTN1	ENST00000850957.1	c.3902A>G	p.Glu1301Gly	missense_variant	Exon 23 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes AF: 0.00251 AC: 382 AN: 152166 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00425

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00236 AC: 592 AN: 251024 AF XY: 0.00237

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00407

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000602

Gnomad NFE exome AF: 0.00392

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00341 AC: 4989 AN: 1461706 Hom.: 21 Cov.: 33 AF XY: 0.00332 AC XY: 2414 AN XY: 727168

African (AFR) AF: 0.000448 AC: 15 AN: 33478

American (AMR) AF: 0.00103 AC: 46 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 98 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00134 AC: 116 AN: 86254

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53350

Middle Eastern (MID) AF: 0.00245 AC: 14 AN: 5718

European-Non Finnish (NFE) AF: 0.00403 AC: 4483 AN: 1111966

Other (OTH) AF: 0.00310 AC: 187 AN: 60384

GnomAD4 genome AF: 0.00251 AC: 382 AN: 152284 Hom.: 1 Cov.: 32 AF XY: 0.00240 AC XY: 179 AN XY: 74462

African (AFR) AF: 0.000481 AC: 20 AN: 41566

American (AMR) AF: 0.00131 AC: 20 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4818

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00425 AC: 289 AN: 68008

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00352 Hom.: 0

Bravo AF: 0.00258

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00232 AC: 282

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00371

EpiControl AF: 0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

ASTN1-related disorder Benign:1

Jul 13, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ASTN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.99	T
PhyloP100		4.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.087
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.022	D
Polyphen		0.24	B
Vest4		0.13
MVP		0.068
MPC		0.29
ClinPred		0.021	T
GERP RS		4.6
gMVP		0.44
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs61756323; hg19: chr1-176833427;