rs3127465

Variant names:

• chr1-244437850-C-T
• rs3127465
• NM_001126.5:c.184-82G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS2	NM_001126.5	MANE Select	c.184-82G>A		intron	N/A	NP_001117.2
	ADSS2	NM_001365073.2		c.184-82G>A		intron	N/A	NP_001352002.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS2	ENST00000366535.4	TSL:1 MANE Select	c.184-82G>A		intron	N/A	ENSP00000355493.3	P30520

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

African (AFR) AF: 0.914 AC: 20036 AN: 21918

American (AMR) AF: 0.821 AC: 34691 AN: 42280

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 17840 AN: 21700

East Asian (EAS) AF: 0.758 AC: 27997 AN: 36944

South Asian (SAS) AF: 0.662 AC: 48101 AN: 72662

European-Finnish (FIN) AF: 0.756 AC: 33795 AN: 44726

Middle Eastern (MID) AF: 0.864 AC: 3986 AN: 4612

European-Non Finnish (NFE) AF: 0.827 AC: 491154 AN: 593954

Other (OTH) AF: 0.826 AC: 34135 AN: 41336

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

African (AFR) AF: 0.911 AC: 37843 AN: 41530

American (AMR) AF: 0.856 AC: 13094 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2890 AN: 3472

East Asian (EAS) AF: 0.783 AC: 4044 AN: 5162

South Asian (SAS) AF: 0.669 AC: 3230 AN: 4826

European-Finnish (FIN) AF: 0.725 AC: 7661 AN: 10572

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56263 AN: 67938

Other (OTH) AF: 0.848 AC: 1787 AN: 2108

Alfa AF: 0.834 Hom.: 221900

Bravo AF: 0.856

Asia WGS AF: 0.770 AC: 2678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.25
PhyloP100		-0.20
Mutation Taster		=11/89	disease causing

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

Other links and lift over

dbSNP: rs3127465; hg19: chr1-244601152;