2-189666375-T-A

Variant names:

• chr2-189666375-T-A
• NM_019048.4:c.243T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019048.4(ASNSD1):​c.243T>A​(p.Ser81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: ASNSD1 NM_019048.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.53

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]

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

ENSG00000286165 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25642484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASNSD1	NM_019048.4	c.243T>A	p.Ser81Arg	missense_variant	Exon 4 of 6	ENST00000260952.9	NP_061921.2
ASDURF	NM_001353493.2	c.*264T>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000607829.6	NP_001340422.1
ASNSD1	NM_001353497.2	c.243T>A	p.Ser81Arg	missense_variant	Exon 3 of 5		NP_001340426.1
ASDURF	NM_001353494.2	c.*317T>A		3_prime_UTR_variant	Exon 4 of 4		NP_001340423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASNSD1	ENST00000260952.9	c.243T>A	p.Ser81Arg	missense_variant	Exon 4 of 6	1	NM_019048.4	ENSP00000260952.4
ASDURF	ENST00000607829.6	c.*264T>A		3_prime_UTR_variant	Exon 4 of 4	2	NM_001353493.2	ENSP00000475224.1
ENSG00000286165	ENST00000606910.5	c.221-821T>A		intron_variant	Intron 3 of 4	3		ENSP00000476091.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.243T>A (p.S81R) alteration is located in exon 4 (coding exon 1) of the ASNSD1 gene. This alteration results from a T to A substitution at nucleotide position 243, causing the serine (S) at amino acid position 81 to be replaced by an arginine (R). 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	0.25
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.080
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.77	P;.
Vest4		0.36
MutPred		0.58		Loss of glycosylation at S81 (P = 0.0468);Loss of glycosylation at S81 (P = 0.0468);
MVP		0.36
MPC		0.30
ClinPred		0.80	D
GERP RS		4.7
Varity_R		0.15
gMVP		0.68

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: chr2-190531101;