Genetic Variant ASNSD1:p.Asn213Asp (chr2-189666769-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 15/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

Variant links:

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]

ASNSD1 links:

ENSG00000286165 (HGNC:):

ENSG00000286165 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.064123094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNSD1	NM_019048.4 link	c.637A>G	p.Asn213Asp	missense_variant	Exon 4 of 6	ENST00000260952.9	NP_061921.2	Q9NWL6-1
ASNSD1	NM_001353497.2 link	c.637A>G	p.Asn213Asp	missense_variant	Exon 3 of 5		NP_001340426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASNSD1	ENST00000260952.9 link	c.637A>G	p.Asn213Asp	missense_variant	Exon 4 of 6	1	NM_019048.4	ENSP00000260952.4	Q9NWL6-1
ENSG00000286165	ENST00000606910.5 link	c.221-427A>G		intron_variant	Intron 3 of 4	3		ENSP00000476091.1	U3KQP1
ASNSD1	ENST00000420250.1 link	c.637A>G	p.Asn213Asp	missense_variant	Exon 3 of 5	5		ENSP00000406790.1	C9IYZ1
ASNSD1	ENST00000607062.5 link	c.21+616A>G		intron_variant	Intron 4 of 5	5		ENSP00000475970.1	U3KQK8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.637A>G (p.N213D) alteration is located in exon 4 (coding exon 1) of the ASNSD1 gene. This alteration results from a A to G substitution at nucleotide position 637, causing the asparagine (N) at amino acid position 213 to be replaced by an aspartic acid (D). 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

0.065

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.64

DANN

Benign

0.87

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.017

Sift

Benign

0.34

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.0010

B;.

Vest4

0.049

MutPred

0.37

Loss of helix (P = 0.0093);Loss of helix (P = 0.0093);

MVP

0.085

MPC

0.12

ClinPred

0.10

GERP RS

-0.39

Varity_R

0.028

gMVP

0.28

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over