chr1-176876579-C-A

Variant names:

• chr1-176876579-C-A
• rs138300101
• NM_004319.3:c.3421G>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.3421G>T​(p.Val1141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V1141M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 2 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=0.17064083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.3421G>T	p.Val1141Leu	missense_variant	Exon 21 of 23	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.3421G>T	p.Val1141Leu	missense_variant	Exon 21 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3421G>T	p.Val1141Leu	missense_variant	Exon 21 of 23	1		ENSP00000356629.3
ASTN1	ENST00000424564.2	c.3421G>T	p.Val1141Leu	missense_variant	Exon 21 of 22	1		ENSP00000395041.2
ASTN1	ENST00000850957.1	c.3445G>T	p.Val1149Leu	missense_variant	Exon 21 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.33
DEOGEN2	Benign	0.034	T;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		3.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.11	N;N;N
REVEL	Benign	0.087
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.64	T;T;T
Polyphen		0.090	B;B;.
Vest4		0.44
MutPred		0.14		Loss of methylation at K1142 (P = 0.0863);Loss of methylation at K1142 (P = 0.0863);Loss of methylation at K1142 (P = 0.0863);
MVP		0.34
MPC		0.25
ClinPred		0.71	D
GERP RS		4.4
gMVP		0.54
Mutation Taster		=66/34	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: rs138300101; hg19: chr1-176845715;