rs35590716

chr14-104728984-G-A

Variant summary

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

The NM_152328.5(ADSS1):c.192+4522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,250 control chromosomes in the GnomAD database, including 926 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 0.11 (926 hom., cov: 33)
• Consequence: ADSS1 NM_152328.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300

Genes affected

ADSS1 (HGNC:20093): (adenylosuccinate synthase 1) This gene encodes a member of the adenylosuccinate synthase family of proteins. The encoded muscle-specific enzyme plays a role in the purine nucleotide cycle by catalyzing the first step in the conversion of inosine monophosphate (IMP) to adenosine monophosphate (AMP). Mutations in this gene may cause adolescent onset distal myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADSS1	NM_152328.5	c.192+4522G>A		intron_variant		ENST00000330877.7
ADSS1	XM_006720026.4	c.192+4522G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADSS1	ENST00000330877.7	c.192+4522G>A		intron_variant		1	NM_152328.5	P1
ADSS1	ENST00000710323.1	c.192+4522G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16660 AN: 152132 Hom.: 923 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.110 AC: 16685 AN: 152250 Hom.: 926 Cov.: 33 AF XY: 0.110 AC XY: 8214 AN XY: 74428

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0158

Gnomad4 SAS AF: 0.0754

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.118

Alfa AF: 0.110 Hom.: 812

Bravo AF: 0.112

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.5
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: rs35590716; hg19: chr14-105195321;