chr1-176882938-T-C

Variant names:

• chr1-176882938-T-C
• rs151246825
• NM_004319.3:c.3283A>G

Variant summary

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

The NM_004319.3(ASTN1):​c.3283A>G​(p.Met1095Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,880 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. M1095L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.60
• Publications: 3 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 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	c.3283A>G	p.Met1095Val	missense_variant	Exon 20 of 23	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.3283A>G	p.Met1095Val	missense_variant	Exon 20 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3283A>G	p.Met1095Val	missense_variant	Exon 20 of 23	1		ENSP00000356629.3
ASTN1	ENST00000424564.2	c.3283A>G	p.Met1095Val	missense_variant	Exon 20 of 22	1		ENSP00000395041.2
ASTN1	ENST00000850957.1	c.3307A>G	p.Met1103Val	missense_variant	Exon 20 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251406 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727242

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 86256

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.99	T
PhyloP100		7.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.62	T;T;T
Polyphen		0.45	B;B;.
Vest4		0.78
MutPred		0.13		Gain of catalytic residue at M1095 (P = 0.0859);Gain of catalytic residue at M1095 (P = 0.0859);Gain of catalytic residue at M1095 (P = 0.0859);
MVP		0.32
MPC		0.71
ClinPred		0.39	T
GERP RS		5.7
gMVP		0.52
Mutation Taster		=74/26	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: rs151246825; hg19: chr1-176852074;