NM_004319.3:c.1302G>A

Variant names:

• chr1-177023540-C-T
• rs10798496
• NM_004319.3:c.1302G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004319.3(ASTN1):​c.1302G>A​(p.Gln434Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,601,130 control chromosomes in the GnomAD database, including 134,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10033 hom., cov: 32)
  • Exomes 𝑓: 0.40 (124830 hom.)
• Consequence: ASTN1 NM_004319.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 10 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.735 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004319.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN1	NM_004319.3	MANE Select	c.1302G>A	p.Gln434Gln	synonymous	Exon 7 of 23	NP_004310.1	O14525-2
	ASTN1	NM_001364856.2		c.1302G>A	p.Gln434Gln	synonymous	Exon 7 of 23	NP_001351785.1	O14525-1
	ASTN1	NM_001286164.2		c.1302G>A	p.Gln434Gln	synonymous	Exon 7 of 23	NP_001273093.1	B1AJS1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN1	ENST00000361833.7	TSL:1 MANE Select	c.1302G>A	p.Gln434Gln	synonymous	Exon 7 of 23	ENSP00000354536.2	O14525-2
	ASTN1	ENST00000367657.7	TSL:1	c.1302G>A	p.Gln434Gln	synonymous	Exon 7 of 23	ENSP00000356629.3	B1AJS1
	ASTN1	ENST00000424564.2	TSL:1	c.1302G>A	p.Gln434Gln	synonymous	Exon 7 of 22	ENSP00000395041.2	O14525-3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52897 AN: 151856 Hom.: 10030 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.00713

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.343 AC: 81568 AN: 237830 AF XY: 0.352

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.00526

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.380

GnomAD4 exome AF: 0.404 AC: 586039 AN: 1449156 Hom.: 124830 Cov.: 44 AF XY: 0.404 AC XY: 291279 AN XY: 720858

African (AFR) AF: 0.261 AC: 8479 AN: 32548

American (AMR) AF: 0.197 AC: 8096 AN: 41120

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 11527 AN: 25552

East Asian (EAS) AF: 0.00237 AC: 93 AN: 39286

South Asian (SAS) AF: 0.330 AC: 27893 AN: 84504

European-Finnish (FIN) AF: 0.418 AC: 22282 AN: 53256

Middle Eastern (MID) AF: 0.466 AC: 2613 AN: 5610

European-Non Finnish (NFE) AF: 0.435 AC: 481701 AN: 1107496

Other (OTH) AF: 0.391 AC: 23355 AN: 59784

GnomAD4 genome AF: 0.348 AC: 52913 AN: 151974 Hom.: 10033 Cov.: 32 AF XY: 0.341 AC XY: 25356 AN XY: 74300

African (AFR) AF: 0.263 AC: 10899 AN: 41458

American (AMR) AF: 0.267 AC: 4084 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1620 AN: 3464

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5180

South Asian (SAS) AF: 0.299 AC: 1433 AN: 4790

European-Finnish (FIN) AF: 0.404 AC: 4262 AN: 10560

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29342 AN: 67924

Other (OTH) AF: 0.357 AC: 754 AN: 2112

Alfa AF: 0.357 Hom.: 7118

Bravo AF: 0.335

Asia WGS AF: 0.132 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.9
DANN	Benign	0.57
PhyloP100		0.73
Mutation Taster		=81/19	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: rs10798496; hg19: chr1-176992676; COSMIC: COSV56069665;