7-97858350-GGC-TGT

Variant names:

• chr7-97858350-GGC-TGT
• NM_001673.5:c.829_831delGCCinsACA
• ASNS p.Ala277Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_001673.5(ASNS):​c.829_831delGCCinsACA​(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. A277A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASNS NM_001673.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• Publications: 0 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ENSG00000284707 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 27 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 1.8574 (below the threshold of 3.09). Trascript score misZ: 2.3971 (below the threshold of 3.09). GenCC associations: The gene is linked to congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001673.5. 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
	ASNS	NM_001673.5	MANE Select	c.829_831delGCCinsACA	p.Ala277Thr	missense	N/A	NP_001664.3
	ASNS	NM_001352496.2		c.829_831delGCCinsACA	p.Ala277Thr	missense	N/A	NP_001339425.1	P08243-1
	ASNS	NM_133436.3		c.829_831delGCCinsACA	p.Ala277Thr	missense	N/A	NP_597680.2	P08243-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNS	ENST00000394308.8	TSL:1 MANE Select	c.829_831delGCCinsACA	p.Ala277Thr	missense	N/A	ENSP00000377845.3	P08243-1
	ASNS	ENST00000175506.8	TSL:1	c.829_831delGCCinsACA	p.Ala277Thr	missense	N/A	ENSP00000175506.4	P08243-1
	ASNS	ENST00000931349.1		c.832_834delGCCinsACA	p.Ala278Thr	missense	N/A	ENSP00000601408.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-97487662;