Variant 3-131024599-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014065.4(ASTE1):c.708A>C(p.Leu236Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,611,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASTE1
NM_014065.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.808

Variant links:

Genes affected

ASTE1 (HGNC:25021): (asteroid homolog 1) Predicted to enable nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. [provided by Alliance of Genome Resources, Apr 2022]

ASTE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026313186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTE1	NM_014065.4 link	c.708A>C	p.Leu236Phe	missense_variant	3/6	ENST00000264992.8	NP_054784.2	Q2TB18-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASTE1	ENST00000264992.8 link	c.708A>C	p.Leu236Phe	missense_variant	3/6	1	NM_014065.4	ENSP00000264992.3	Q2TB18-1
ASTE1	ENST00000514044.5 link	c.708A>C	p.Leu236Phe	missense_variant	3/7	1		ENSP00000426421.1	D6RG30
ASTE1	ENST00000507978.5 link	n.708A>C		non_coding_transcript_exon_variant	3/7	2		ENSP00000421019.1	Q2TB18-2
ASTE1	ENST00000504964.1 link	n.144-361A>C		intron_variant		3		ENSP00000426363.1	D6RGH3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249216

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134752

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459440

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725942

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.708A>C (p.L236F) alteration is located in exon 3 (coding exon 1) of the ASTE1 gene. This alteration results from a A to C substitution at nucleotide position 708, causing the leucine (L) at amino acid position 236 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.75

DANN

Benign

0.67

DEOGEN2

Benign

0.0035

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

.;L

PrimateAI

Benign

0.34

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.034

Sift

Benign

0.72

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0020

B;B

Vest4

0.099

MutPred

0.36

Loss of ubiquitination at K238 (P = 0.1296);Loss of ubiquitination at K238 (P = 0.1296);

MVP

0.13

MPC

0.17

ClinPred

0.020

GERP RS

-5.9

Varity_R

0.041

gMVP

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over