1-244449682-T-C

Variant names:

• chr1-244449682-T-C
• rs3003211
• NM_001126.5:c.183+1953A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001126.5(ADSS2):​c.183+1953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,094 control chromosomes in the GnomAD database, including 9,323 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 0.35 (9323 hom., cov: 33)
• Consequence: ADSS2 NM_001126.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADSS2	NM_001126.5	c.183+1953A>G		intron_variant	Intron 1 of 12	ENST00000366535.4	NP_001117.2
ADSS2	NM_001365073.2	c.183+1953A>G		intron_variant	Intron 1 of 12		NP_001352002.1
ADSS2	XM_047447581.1	c.3+308A>G		intron_variant	Intron 2 of 13		XP_047303537.1
ADSS2	XM_047447585.1	c.3+2329A>G		intron_variant	Intron 1 of 12		XP_047303541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADSS2	ENST00000366535.4	c.183+1953A>G		intron_variant	Intron 1 of 12	1	NM_001126.5	ENSP00000355493.3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52854 AN: 151976 Hom.: 9304 Cov.: 33

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.348 AC: 52922 AN: 152094 Hom.: 9323 Cov.: 33 AF XY: 0.350 AC XY: 26000 AN XY: 74346

African (AFR) AF: 0.357 AC: 14782 AN: 41464

American (AMR) AF: 0.359 AC: 5490 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1562 AN: 5180

South Asian (SAS) AF: 0.288 AC: 1388 AN: 4824

European-Finnish (FIN) AF: 0.384 AC: 4054 AN: 10570

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23451 AN: 67984

Other (OTH) AF: 0.357 AC: 753 AN: 2108

Alfa AF: 0.344 Hom.: 5106

Bravo AF: 0.347

Asia WGS AF: 0.332 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.57
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3003211; hg19: chr1-244612984;