2-189666724-C-A

Variant names:

• chr2-189666724-C-A
• NM_019048.4:c.592C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019048.4(ASNSD1):​c.592C>A​(p.Pro198Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ASNSD1 NM_019048.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNSD1	NM_019048.4	c.592C>A	p.Pro198Thr	missense_variant	Exon 4 of 6	ENST00000260952.9	NP_061921.2
ASNSD1	NM_001353497.2	c.592C>A	p.Pro198Thr	missense_variant	Exon 3 of 5		NP_001340426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASNSD1	ENST00000260952.9	c.592C>A	p.Pro198Thr	missense_variant	Exon 4 of 6	1	NM_019048.4	ENSP00000260952.4
ENSG00000286165	ENST00000606910.5	c.221-472C>A		intron_variant	Intron 3 of 4	3		ENSP00000476091.1
ASNSD1	ENST00000420250.1	c.592C>A	p.Pro198Thr	missense_variant	Exon 3 of 5	5		ENSP00000406790.1
ASNSD1	ENST00000607062.5	c.21+571C>A		intron_variant	Intron 4 of 5	5		ENSP00000475970.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.592C>A (p.P198T) alteration is located in exon 4 (coding exon 1) of the ASNSD1 gene. This alteration results from a C to A substitution at nucleotide position 592, causing the proline (P) at amino acid position 198 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		1.0	D;.
Vest4		0.33
MutPred		0.56		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.38
MPC		0.44
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.54
gMVP		0.81

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-190531450;