rs3127465

Positions:

• chr1-244437850-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001126.5(ADSS2):​c.184-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 1,032,232 control chromosomes in the GnomAD database, including 343,737 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (54056 hom., cov: 31)
  • Exomes 𝑓: 0.81 (289681 hom.)
• Consequence: ADSS2 NM_001126.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

Genes affected

ADSS2 (HGNC:292): (adenylosuccinate synthase 2) This gene encodes the enzyme adenylosuccinate synthetase which catalyzes the first committed step in the conversion of inosine monophosphate to adenosine monophosphate. A pseudogene of this gene is found on chromosome 17.[provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADSS2	NM_001126.5	c.184-82G>A		intron_variant		ENST00000366535.4	NP_001117.2
ADSS2	NM_001365073.2	c.184-82G>A		intron_variant			NP_001352002.1
ADSS2	XM_047447581.1	c.4-82G>A		intron_variant			XP_047303537.1
ADSS2	XM_047447585.1	c.4-82G>A		intron_variant			XP_047303541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADSS2	ENST00000366535.4	c.184-82G>A		intron_variant		1	NM_001126.5	ENSP00000355493.3

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127703 AN: 151982 Hom.: 54014 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.849

GnomAD4 exome AF: 0.809 AC: 711735 AN: 880132 Hom.: 289681 AF XY: 0.803 AC XY: 369749 AN XY: 460568

Gnomad4 AFR exome AF: 0.914

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.822

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.756

Gnomad4 NFE exome AF: 0.827

Gnomad4 OTH exome AF: 0.826

GnomAD4 genome AF: 0.840 AC: 127800 AN: 152100 Hom.: 54056 Cov.: 31 AF XY: 0.832 AC XY: 61845 AN XY: 74332

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.848

Alfa AF: 0.833 Hom.: 105798

Bravo AF: 0.856

Asia WGS AF: 0.770 AC: 2678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.25

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

LitVar

Other links and lift over

dbSNP: rs3127465; hg19: chr1-244601152;