NM_019048.4:c.361T>C

Variant names:

• chr2-189666493-T-C
• NM_019048.4:c.361T>C

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.361T>C​(p.Phe121Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASNSD1 NM_019048.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• 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, 0.894

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.361T>C	p.Phe121Leu	missense	Exon 4 of 6	NP_061921.2	Q9NWL6-1
	ASNSD1	NM_001353497.2		c.361T>C	p.Phe121Leu	missense	Exon 3 of 5	NP_001340426.1	Q9NWL6-1
	ASDURF	NM_001353493.2	MANE Select	c.*382T>C		downstream_gene	N/A	NP_001340422.1	L0R819-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASNSD1	ENST00000260952.9	TSL:1 MANE Select	c.361T>C	p.Phe121Leu	missense	Exon 4 of 6	ENSP00000260952.4	Q9NWL6-1
	ENSG00000286165	ENST00000606910.5	TSL:3	c.221-703T>C		intron	N/A	ENSP00000476091.1	U3KQP1
	ASNSD1	ENST00000420250.1	TSL:5	c.361T>C	p.Phe121Leu	missense	Exon 3 of 5	ENSP00000406790.1	C9IYZ1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.010	D
Sift4G	Benign	0.066	T
Polyphen		1.0	D
Vest4		0.84
MutPred		0.80		Loss of catalytic residue at F121 (P = 0.2643)
MVP		0.35
MPC		0.49
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.48
gMVP		0.83
Mutation Taster		=50/50

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

hg19: chr2-190531219;