7-97858834-GTTT-GTTTT

Variant names:

• chr7-97858834-G-GT
• rs36021744
• NM_001673.5:c.775+19dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001673.5(ASNS):​c.775+19dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,586,306 control chromosomes in the GnomAD database, including 70,537 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6067 hom., cov: 21)
  • Exomes 𝑓: 0.29 (64470 hom.)
• Consequence: ASNS NM_001673.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0440
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000284707 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-97858834-G-GT is Benign according to our data. Variant chr7-97858834-G-GT is described in ClinVar as Benign. ClinVar VariationId is 680024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNS	NM_001673.5	c.775+19dupA		intron_variant	Intron 6 of 12	ENST00000394308.8	NP_001664.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASNS	ENST00000394308.8	c.775+19_775+20insA		intron_variant	Intron 6 of 12	1	NM_001673.5	ENSP00000377845.3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40951 AN: 151890 Hom.: 6072 Cov.: 21

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.286

GnomAD2 exomes AF: 0.325 AC: 75984 AN: 233956 AF XY: 0.327

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.471

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.422

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.291 AC: 417543 AN: 1434298 Hom.: 64470 Cov.: 30 AF XY: 0.295 AC XY: 210420 AN XY: 713892

African (AFR) AF: 0.154 AC: 4953 AN: 32138

American (AMR) AF: 0.459 AC: 18053 AN: 39294

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 7559 AN: 25226

East Asian (EAS) AF: 0.394 AC: 15551 AN: 39458

South Asian (SAS) AF: 0.440 AC: 36097 AN: 82052

European-Finnish (FIN) AF: 0.235 AC: 12448 AN: 53076

Middle Eastern (MID) AF: 0.351 AC: 1968 AN: 5602

European-Non Finnish (NFE) AF: 0.276 AC: 303471 AN: 1098156

Other (OTH) AF: 0.294 AC: 17443 AN: 59296

GnomAD4 genome AF: 0.269 AC: 40955 AN: 152008 Hom.: 6067 Cov.: 21 AF XY: 0.275 AC XY: 20416 AN XY: 74302

African (AFR) AF: 0.159 AC: 6585 AN: 41462

American (AMR) AF: 0.412 AC: 6289 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1105 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2149 AN: 5160

South Asian (SAS) AF: 0.446 AC: 2143 AN: 4808

European-Finnish (FIN) AF: 0.243 AC: 2568 AN: 10548

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19218 AN: 67968

Other (OTH) AF: 0.284 AC: 599 AN: 2110

Alfa AF: 0.200 Hom.: 663

Bravo AF: 0.274

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 72% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 67. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.044
Mutation Taster		=100/0	polymorphism (auto)

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: rs36021744; hg19: chr7-97488146;