1-176864350-C-A

Variant names:

• chr1-176864350-C-A
• rs61758730
• NM_004319.3:c.3819G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004319.3(ASTN1):​c.3819G>T​(p.Arg1273Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10267195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.3819G>T	p.Arg1273Ser	missense_variant	Exon 23 of 23	ENST00000361833.7	NP_004310.1
ASTN1	NM_001364856.2	c.3843G>T	p.Arg1281Ser	missense_variant	Exon 23 of 23		NP_001351785.1
ASTN1	NM_001286164.2	c.3647+4494G>T		intron_variant	Intron 22 of 22		NP_001273093.1
ASTN1	XM_017001341.3	c.3671+4494G>T		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.3819G>T	p.Arg1273Ser	missense_variant	Exon 23 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3647+4494G>T		intron_variant	Intron 22 of 22	1		ENSP00000356629.3
ASTN1	ENST00000850957.1	c.3843G>T	p.Arg1281Ser	missense_variant	Exon 23 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.00082
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.073
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		0.030	B
Vest4		0.32
MutPred		0.28		Loss of helix (P = 0.0626);
MVP		0.082
MPC		0.28
ClinPred		0.83	D
GERP RS		3.6
gMVP		0.43
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs61758730; hg19: chr1-176833486;