1-177023540-C-A

Variant names:

• chr1-177023540-C-A
• rs10798496
• NM_004319.3:c.1302G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004319.3(ASTN1):​c.1302G>T​(p.Gln434His) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 10 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29926974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004319.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN1	NM_004319.3	MANE Select	c.1302G>T	p.Gln434His	missense	Exon 7 of 23	NP_004310.1	O14525-2
	ASTN1	NM_001364856.2		c.1302G>T	p.Gln434His	missense	Exon 7 of 23	NP_001351785.1	O14525-1
	ASTN1	NM_001286164.2		c.1302G>T	p.Gln434His	missense	Exon 7 of 23	NP_001273093.1	B1AJS1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTN1	ENST00000361833.7	TSL:1 MANE Select	c.1302G>T	p.Gln434His	missense	Exon 7 of 23	ENSP00000354536.2	O14525-2
	ASTN1	ENST00000367657.7	TSL:1	c.1302G>T	p.Gln434His	missense	Exon 7 of 23	ENSP00000356629.3	B1AJS1
	ASTN1	ENST00000424564.2	TSL:1	c.1302G>T	p.Gln434His	missense	Exon 7 of 22	ENSP00000395041.2	O14525-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.73
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.22
Sift	Benign	0.23	T
Sift4G	Benign	0.59	T
Polyphen		0.023	B
Vest4		0.28
MutPred		0.25		Gain of loop (P = 0.1069)
MVP		0.72
MPC		0.82
ClinPred		0.69	D
GERP RS		2.7
gMVP		0.68
Mutation Taster		=64/36	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: rs10798496; hg19: chr1-176992676;