rs6644

chr14-104747006-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152328.5(ADSS1):c.*3A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,612,700 control chromosomes in the GnomAD database, including 206,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (30761 hom., cov: 33)
  • Exomes 𝑓: 0.48 (175747 hom.)
• Consequence: ADSS1 NM_152328.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-104747006-A-G is Benign according to our data. Variant chr14-104747006-A-G is described in ClinVar as [Benign]. Clinvar id is 1189017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADSS1	NM_152328.5	c.*3A>G		3_prime_UTR_variant	13/13	ENST00000330877.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADSS1	ENST00000330877.7	c.*3A>G		3_prime_UTR_variant	13/13	1	NM_152328.5	P1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92237 AN: 152036 Hom.: 30714 Cov.: 33

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.583

GnomAD3 exomes AF: 0.547 AC: 137562 AN: 251342 Hom.: 39917 AF XY: 0.534 AC XY: 72594 AN XY: 135842

Gnomad AFR exome AF: 0.895

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.631

Gnomad SAS exome AF: 0.579

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.482 AC: 703779 AN: 1460546 Hom.: 175747 Cov.: 39 AF XY: 0.482 AC XY: 350154 AN XY: 726502

Gnomad4 AFR exome AF: 0.908

Gnomad4 AMR exome AF: 0.678

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.450

Gnomad4 OTH exome AF: 0.508

GnomAD4 genome AF: 0.607 AC: 92339 AN: 152154 Hom.: 30761 Cov.: 33 AF XY: 0.609 AC XY: 45334 AN XY: 74384

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.498

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.584

Alfa AF: 0.499 Hom.: 25831

Bravo AF: 0.630

Asia WGS AF: 0.653 AC: 2272 AN: 3478

EpiCase AF: 0.471

EpiControl AF: 0.459

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Myopathy, distal, 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.11
Dann	Benign	0.34

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: rs6644; hg19: chr14-105213343; COSMIC: COSV58273773; COSMIC: COSV58273773;