NM_019048.4:c.637A>G

Variant names:

• chr2-189666769-A-G
• rs1188644028
• NM_019048.4:c.637A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019048.4(ASNSD1):​c.637A>G​(p.Asn213Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ASNSD1 NM_019048.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.145
• 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:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064123094).

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.637A>G	p.Asn213Asp	missense	Exon 4 of 6	NP_061921.2	Q9NWL6-1
	ASNSD1	NM_001353497.2		c.637A>G	p.Asn213Asp	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.637A>G	p.Asn213Asp	missense	Exon 4 of 6	ENSP00000260952.4	Q9NWL6-1
	ENSG00000286165	ENST00000606910.5	TSL:3	c.221-427A>G		intron	N/A	ENSP00000476091.1	U3KQP1
	ASNSD1	ENST00000420250.1	TSL:5	c.637A>G	p.Asn213Asp	missense	Exon 3 of 5	ENSP00000406790.1	C9IYZ1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461528 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111722

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.64
DANN	Benign	0.87
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.017
Sift	Benign	0.34	T
Sift4G	Benign	0.71	T
Polyphen		0.0010	B
Vest4		0.049
MutPred		0.37		Loss of helix (P = 0.0093)
MVP		0.085
MPC		0.12
ClinPred		0.10	T
GERP RS		-0.39
Varity_R		0.028
gMVP		0.28
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1188644028; hg19: chr2-190531495;