rs759502995

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-176894732-G-A
• chr1-176894732-G-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.2770C>T​(p.His924Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ASTN1 NM_004319.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.13425699).

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.2770C>T	p.His924Tyr	missense	Exon 17 of 23	NP_004310.1	O14525-2
	ASTN1	NM_001364856.2		c.2794C>T	p.His932Tyr	missense	Exon 17 of 23	NP_001351785.1	O14525-1
	ASTN1	NM_001286164.2		c.2770C>T	p.His924Tyr	missense	Exon 17 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.2770C>T	p.His924Tyr	missense	Exon 17 of 23	ENSP00000354536.2	O14525-2
	ASTN1	ENST00000367657.7	TSL:1	c.2770C>T	p.His924Tyr	missense	Exon 17 of 23	ENSP00000356629.3	B1AJS1
	ASTN1	ENST00000424564.2	TSL:1	c.2770C>T	p.His924Tyr	missense	Exon 17 of 22	ENSP00000395041.2	O14525-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251376 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461802 Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9 AN XY: 727208

African (AFR) AF: 0.0000299 AC: 1 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: 0.0000216 AC: 24 AN: 1111994

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Abnormal corpus callosum morphology (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		7.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.14
Sift	Uncertain	0.010	D
Sift4G	Benign	0.092	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.13		Gain of phosphorylation at H924 (P = 0.0184)
MVP		0.043
MPC		0.28
ClinPred		0.32	T
GERP RS		5.3
gMVP		0.41
Mutation Taster		=59/41	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; COSMIC: COSV62495918;