1-176868976-T-A

Variant names:

• chr1-176868976-T-A
• rs1553217993
• NM_004319.3:c.3515A>T

Variant summary

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

The NM_004319.3(ASTN1):​c.3515A>T​(p.Glu1172Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 7.99
• Publications: 0 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.3515A>T	p.Glu1172Val	missense_variant	Exon 22 of 23	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.3515A>T	p.Glu1172Val	missense_variant	Exon 22 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3515A>T	p.Glu1172Val	missense_variant	Exon 22 of 23	1		ENSP00000356629.3
ASTN1	ENST00000424564.2	c.3515A>T	p.Glu1172Val	missense_variant	Exon 22 of 22	1		ENSP00000395041.2
ASTN1	ENST00000850957.1	c.3539A>T	p.Glu1180Val	missense_variant	Exon 22 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.98	T
PhyloP100		8.0
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.92
MutPred		0.20		Loss of disorder (P = 0.0103);Loss of disorder (P = 0.0103);Loss of disorder (P = 0.0103);
MVP		0.39
MPC		0.91
ClinPred		0.94	D
GERP RS		5.7
gMVP		0.84
Mutation Taster		=47/53	disease causing

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: rs1553217993; hg19: chr1-176838112;