NM_004319.3:c.3412G>T

Variant names:

• chr1-176876588-C-A
• rs778027121
• NM_004319.3:c.3412G>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.3412G>T​(p.Asp1138Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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. D1138N) 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: 3.81
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30641955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.3412G>T	p.Asp1138Tyr	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.3412G>T	p.Asp1138Tyr	missense_variant	Exon 21 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.3412G>T	p.Asp1138Tyr	missense_variant	Exon 21 of 23	1		ENSP00000356629.3
ASTN1	ENST00000424564.2	c.3412G>T	p.Asp1138Tyr	missense_variant	Exon 21 of 22	1		ENSP00000395041.2
ASTN1	ENST00000850957.1	c.3436G>T	p.Asp1146Tyr	missense_variant	Exon 21 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T;.;.
Eigen	Benign	-0.013
Eigen_PC	Benign	0.031
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		3.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.25	T;T;T
Sift4G	Uncertain	0.058	T;T;T
Polyphen		0.75	P;P;.
Vest4		0.54
MutPred		0.30		Gain of catalytic residue at D1138 (P = 0.0111);Gain of catalytic residue at D1138 (P = 0.0111);Gain of catalytic residue at D1138 (P = 0.0111);
MVP		0.19
MPC		0.56
ClinPred		0.79	D
GERP RS		5.2
gMVP		0.72
Mutation Taster		=61/39	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: rs778027121; hg19: chr1-176845724;