chr2-189666661-G-A

Variant names:

• chr2-189666661-G-A
• NM_019048.4:c.529G>A
• ASNSD1 p.Gly177Arg

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019048.4(ASNSD1):​c.529G>A​(p.Gly177Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASNSD1 NM_019048.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.47
• Publications: 0 publications found

Genes affected

ASNSD1 (HGNC:24910): (asparagine synthetase domain containing 1) Predicted to enable asparagine synthase (glutamine-hydrolyzing) activity. Predicted to be involved in asparagine biosynthetic process and glutamine metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286165 (HGNC:):

ASDURF (HGNC:53619): (ASNSD1 upstream open reading frame) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.893

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019048.4. 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
	ASNSD1	NM_019048.4	MANE Select	c.529G>A	p.Gly177Arg	missense	Exon 4 of 6	NP_061921.2	Q9NWL6-1
	ASNSD1	NM_001353497.2		c.529G>A	p.Gly177Arg	missense	Exon 3 of 5	NP_001340426.1	Q9NWL6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNSD1	ENST00000260952.9	TSL:1 MANE Select	c.529G>A	p.Gly177Arg	missense	Exon 4 of 6	ENSP00000260952.4	Q9NWL6-1
	ENSG00000286165	ENST00000606910.5	TSL:3	c.221-535G>A		intron	N/A	ENSP00000476091.1	U3KQP1
	ASNSD1	ENST00000420250.1	TSL:5	c.529G>A	p.Gly177Arg	missense	Exon 3 of 5	ENSP00000406790.1	C9IYZ1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.014	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		9.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Varity_R		0.83
gMVP		0.89
Mutation Taster		=7/93	disease causing

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

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

Other links and lift over

hg19: chr2-190531387;