NM_004319.3:c.3825G>A

Variant names:

• chr1-176864344-C-T
• rs144824957
• NM_004319.3:c.3825G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004319.3(ASTN1):​c.3825G>A​(p.Thr1275Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,614,124 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (18 hom.)
• Consequence: ASTN1 NM_004319.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -8.44
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-176864344-C-T is Benign according to our data. Variant chr1-176864344-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2639586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-8.44 with no splicing effect.
• 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	c.3825G>A	p.Thr1275Thr	synonymous_variant	Exon 23 of 23	ENST00000361833.7	NP_004310.1
ASTN1	NM_001364856.2	c.3849G>A	p.Thr1283Thr	synonymous_variant	Exon 23 of 23		NP_001351785.1
ASTN1	NM_001286164.2	c.3647+4500G>A		intron_variant	Intron 22 of 22		NP_001273093.1
ASTN1	XM_017001341.3	c.3671+4500G>A		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.3825G>A	p.Thr1275Thr	synonymous_variant	Exon 23 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3647+4500G>A		intron_variant	Intron 22 of 22	1		ENSP00000356629.3
ASTN1	ENST00000850957.1	c.3849G>A	p.Thr1283Thr	synonymous_variant	Exon 23 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes AF: 0.00275 AC: 419 AN: 152144 Hom.: 4 Cov.: 32

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: 0.00745

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00352 AC: 885 AN: 251236 AF XY: 0.00384

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.0110

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00398

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00384 AC: 5611 AN: 1461862 Hom.: 18 Cov.: 32 AF XY: 0.00396 AC XY: 2880 AN XY: 727240

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.00136 AC: 61 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00976 AC: 255 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00714 AC: 616 AN: 86258

European-Finnish (FIN) AF: 0.000861 AC: 46 AN: 53416

Middle Eastern (MID) AF: 0.00746 AC: 43 AN: 5766

European-Non Finnish (NFE) AF: 0.00392 AC: 4359 AN: 1111992

Other (OTH) AF: 0.00364 AC: 220 AN: 60394

GnomAD4 genome AF: 0.00275 AC: 419 AN: 152262 Hom.: 4 Cov.: 32 AF XY: 0.00250 AC XY: 186 AN XY: 74446

African (AFR) AF: 0.000602 AC: 25 AN: 41540

American (AMR) AF: 0.00105 AC: 16 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00746 AC: 36 AN: 4826

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00401 AC: 273 AN: 68014

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00360 Hom.: 1

Bravo AF: 0.00251

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-8.4
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144824957; hg19: chr1-176833480; COSMIC: COSV62490495; COSMIC: COSV62490495;