rs35590716

Variant names:

• chr14-104728984-G-A
• rs35590716
• NM_152328.5:c.192+4522G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ADSS1 Gene-Disease associations (from GenCC):

• myopathy, distal, 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADSS1	NM_152328.5	c.192+4522G>A		intron_variant	Intron 1 of 12	ENST00000330877.7	NP_689541.1
ADSS1	XM_006720026.4	c.192+4522G>A		intron_variant	Intron 1 of 13		XP_006720089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADSS1	ENST00000330877.7	c.192+4522G>A		intron_variant	Intron 1 of 12	1	NM_152328.5	ENSP00000331260.2
ADSS1	ENST00000710323.1	c.192+4522G>A		intron_variant	Intron 1 of 12			ENSP00000518203.1

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

African (AFR) AF: 0.108 AC: 4470 AN: 41522

American (AMR) AF: 0.119 AC: 1828 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5184

South Asian (SAS) AF: 0.0754 AC: 364 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1264 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8013 AN: 68030

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.110 Hom.: 1052

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
PhyloP100		-0.030
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: rs35590716; hg19: chr14-105195321;