rs3127460

Positions:

• chr1-244427040-T-A
• chr1-244427040-T-C

Variant summary

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

The NM_001126.5(ADSS2):​c.407-2653A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,080 control chromosomes in the GnomAD database, including 54,012 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 (54012 hom., cov: 31)
• Consequence: ADSS2 NM_001126.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADSS2	NM_001126.5	c.407-2653A>T		intron_variant		ENST00000366535.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADSS2	ENST00000366535.4	c.407-2653A>T		intron_variant		1	NM_001126.5	P1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127661 AN: 151962 Hom.: 53973 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.849

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.840 AC: 127755 AN: 152080 Hom.: 54012 Cov.: 31 AF XY: 0.832 AC XY: 61825 AN XY: 74328

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.724

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.848

Alfa AF: 0.832 Hom.: 6158

Bravo AF: 0.856

Asia WGS AF: 0.768 AC: 2670 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.8
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs3127460; hg19: chr1-244590342;