NM_004319.3:c.2770C>A

Variant names:

• chr1-176894732-G-T
• rs759502995
• NM_004319.3:c.2770C>A

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.2770C>A​(p.His924Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. H924Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1516667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASTN1	NM_004319.3	c.2770C>A	p.His924Asn	missense_variant	Exon 17 of 23	ENST00000361833.7	NP_004310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASTN1	ENST00000361833.7	c.2770C>A	p.His924Asn	missense_variant	Exon 17 of 23	1	NM_004319.3	ENSP00000354536.2
ASTN1	ENST00000367657.7	c.2770C>A	p.His924Asn	missense_variant	Exon 17 of 23	1		ENSP00000356629.3
ASTN1	ENST00000424564.2	c.2770C>A	p.His924Asn	missense_variant	Exon 17 of 22	1		ENSP00000395041.2
ASTN1	ENST00000850957.1	c.2794C>A	p.His932Asn	missense_variant	Exon 17 of 23			ENSP00000521041.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

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	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;.;.
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		7.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.050	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.053	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.21
MutPred		0.045		Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);
MVP		0.16
MPC		0.27
ClinPred		0.90	D
GERP RS		5.3
gMVP		0.40
Mutation Taster		=57/43	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: rs759502995; hg19: chr1-176863868;