rs778485570

Variant names:

• chr1-176864438-C-A
• rs778485570
• NM_004319.3:c.3731G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-176864438-C-A
• chr1-176864438-C-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.3731G>T​(p.Arg1244Leu) 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. R1244Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 1 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=0.23102784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.3731G>T	p.Arg1244Leu	missense_variant	Exon 23 of 23	ENST00000361833.7	NP_004310.1
ASTN1	NM_001364856.2	c.3755G>T	p.Arg1252Leu	missense_variant	Exon 23 of 23		NP_001351785.1
ASTN1	NM_001286164.2	c.3647+4406G>T		intron_variant	Intron 22 of 22		NP_001273093.1
ASTN1	XM_017001341.3	c.3671+4406G>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.3731G>T	p.Arg1244Leu	missense_variant	Exon 23 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3647+4406G>T		intron_variant	Intron 22 of 22	1		ENSP00000356629.3
ASTN1	ENST00000850957.1	c.3755G>T	p.Arg1252Leu	missense_variant	Exon 23 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	-0.088
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.28	B
Vest4		0.40
MutPred		0.56		Loss of MoRF binding (P = 0.0331);
MVP		0.23
MPC		0.33
ClinPred		0.83	D
GERP RS		3.4
gMVP		0.64
Mutation Taster		=85/15	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: rs778485570; hg19: chr1-176833574;