rs2070159

Positions:

chr7-97858352-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001673.5(ASNS):c.829G>A(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,614,120 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 22 hom. )

Consequence

ASNS
NM_001673.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.734

Variant links:

Genes affected

ASNS (HGNC:753): (asparagine synthetase (glutamine-hydrolyzing)) The protein encoded by this gene is involved in the synthesis of asparagine. This gene complements a mutation in the temperature-sensitive hamster mutant ts11, which blocks progression through the G1 phase of the cell cycle at nonpermissive temperature. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]

ASNS links:

CZ1P-ASNS (HGNC:):

CZ1P-ASNS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036463737).

BP6

Variant 7-97858352-C-T is Benign according to our data. Variant chr7-97858352-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00935 (1424/152286) while in subpopulation AFR AF= 0.0329 (1367/41544). AF 95% confidence interval is 0.0315. There are 17 homozygotes in gnomad4. There are 695 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASNS	NM_001673.5 linkuse as main transcript	c.829G>A	p.Ala277Thr	missense_variant	7/13	ENST00000394308.8	NP_001664.3
CZ1P-ASNS	NR_147989.1 linkuse as main transcript	n.2458G>A		non_coding_transcript_exon_variant	13/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASNS	ENST00000394308.8 linkuse as main transcript	c.829G>A	p.Ala277Thr	missense_variant	7/13	1	NM_001673.5	ENSP00000377845	P1	P08243-1

Frequencies

GnomAD3 genomes

AF:

0.00936

AC:

1424

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00252

AC:

634

AN:

251402

Hom.:

AF XY:

0.00188

AC XY:

255

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0341

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00100

AC:

1467

AN:

1461834

Hom.:

Cov.:

AF XY:

0.000914

AC XY:

665

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0317

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00935

AC:

1424

AN:

152286

Hom.:

Cov.:

AF XY:

0.00933

AC XY:

695

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.0107

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0336

AC:

148

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00322

AC:

391

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 31, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 23, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.41

T;T;.;T;.;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.62

T;.;.;.;.;T;T

MetaRNN

Benign

0.0036

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

L;L;.;L;.;.;.

MutationTaster

Benign

0.82

D;D;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.23

N;N;N;N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.56

T;T;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;T;T

Polyphen

0.24

B;B;.;B;.;.;.

Vest4

0.11

MVP

0.52

MPC

0.40

ClinPred

0.0049

GERP RS

2.5

Varity_R

0.029

gMVP

0.38

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