Variant 2-189666245-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000260952.9(ASNSD1):c.113T>C(p.Leu38Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ASNSD1
ENST00000260952.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

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:

ASDURF (HGNC:53619): (ASNSD1 upstream open reading frame) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ASDURF links:

ENSG00000286165 (HGNC:):

ENSG00000286165 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
ASNSD1	NM_019048.4 linkuse as main transcript	c.113T>C	p.Leu38Ser	missense_variant	4/6	ENST00000260952.9	NP_061921.2	Q9NWL6-1
ASDURF	NM_001353493.2 linkuse as main transcript	c.*134T>C		3_prime_UTR_variant	4/4	ENST00000607829.6	NP_001340422.1
ASNSD1	NM_001353497.2 linkuse as main transcript	c.113T>C	p.Leu38Ser	missense_variant	3/5		NP_001340426.1
ASDURF	NM_001353494.2 linkuse as main transcript	c.*187T>C		3_prime_UTR_variant	4/4		NP_001340423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASNSD1	ENST00000260952.9 linkuse as main transcript	c.113T>C	p.Leu38Ser	missense_variant	4/6	1	NM_019048.4	ENSP00000260952.4	Q9NWL6-1
ASDURF	ENST00000607829.6 linkuse as main transcript	c.*134T>C		3_prime_UTR_variant	4/4	2	NM_001353493.2	ENSP00000475224.1	L0R819-1
ENSG00000286165	ENST00000606910.5 linkuse as main transcript	c.220+794T>C		intron_variant		3		ENSP00000476091.1	U3KQP1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251338

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135838

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Oct 03, 2022

The c.113T>C (p.L38S) alteration is located in exon 4 (coding exon 1) of the ASNSD1 gene. This alteration results from a T to C substitution at nucleotide position 113, causing the leucine (L) at amino acid position 38 to be replaced by a serine (S). 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

0.26

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.5

N;D;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.0050

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.75

MutPred

0.61

Loss of stability (P = 0.0081);Loss of stability (P = 0.0081);Loss of stability (P = 0.0081);

MVP

0.38

MPC

0.39

ClinPred

0.80

GERP RS

5.8

Varity_R

0.24

gMVP

0.85

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