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 (★★). Synonymous variant affecting the same amino acid position (i.e. A277A) has been classified 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

1
17

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

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]

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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 UniProt
ASNSNM_001673.5 linkuse as main transcriptc.829G>A p.Ala277Thr missense_variant 7/13 ENST00000394308.8
CZ1P-ASNSNR_147989.1 linkuse as main transcriptn.2458G>A non_coding_transcript_exon_variant 13/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASNSENST00000394308.8 linkuse as main transcriptc.829G>A p.Ala277Thr missense_variant 7/131 NM_001673.5 P1P08243-1

Frequencies

GnomAD3 genomes
AF:
0.00936
AC:
1424
AN:
152168
Hom.:
18
Cov.:
32
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.:
10
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.:
22
Cov.:
30
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.:
17
Cov.:
32
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.:
6
Bravo
AF:
0.0107
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.0336
AC:
148
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.00322
AC:
391
Asia WGS
AF:
0.00202
AC:
8
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000296

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 31, 2020- -
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsFeb 23, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
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
D
LIST_S2
Benign
0.62
T;.;.;.;.;T;T
MetaRNN
Benign
0.0036
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.94
L;L;.;L;.;.;.
MutationTaster
Benign
0.82
D;D;N;N;N;N;N
PrimateAI
Benign
0.39
T
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
T
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.

Other links and lift over

dbSNP: rs2070159; hg19: chr7-97487664; API