Variant 2-189666620-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019048.4(ASNSD1):c.488C>T(p.Thr163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,822 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: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ASNSD1
NM_019048.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.859

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:

Genome browser will be placed here

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=0.039879322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASNSD1	NM_019048.4 linkuse as main transcript	c.488C>T	p.Thr163Ile	missense_variant	4/6	ENST00000260952.9	NP_061921.2
ASNSD1	NM_001353497.2 linkuse as main transcript	c.488C>T	p.Thr163Ile	missense_variant	3/5		NP_001340426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASNSD1	ENST00000260952.9 linkuse as main transcript	c.488C>T	p.Thr163Ile	missense_variant	4/6	1	NM_019048.4	ENSP00000260952	P1	Q9NWL6-1
ASNSD1	ENST00000420250.1 linkuse as main transcript	c.488C>T	p.Thr163Ile	missense_variant	3/5	5		ENSP00000406790
ASNSD1	ENST00000607062.5 linkuse as main transcript	c.21+467C>T		intron_variant		5		ENSP00000475970

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250598

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727200

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.488C>T (p.T163I) alteration is located in exon 4 (coding exon 1) of the ASNSD1 gene. This alteration results from a C to T substitution at nucleotide position 488, causing the threonine (T) at amino acid position 163 to be replaced by an isoleucine (I). 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

0.076

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.30

DANN

Benign

0.73

DEOGEN2

Benign

0.0047

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.020

Sift

Benign

0.25

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.0

B;.

Vest4

0.057

MutPred

0.40

Loss of disorder (P = 0.0277);Loss of disorder (P = 0.0277);

MVP

0.030

MPC

0.11

ClinPred

0.019

GERP RS

-1.6

Varity_R

0.030

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over