Variant 14-104729893-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001320424.1(ADSS1):c.-727A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 104,930 control chromosomes in the GnomAD database, including 6,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 6049 hom., cov: 23)

Exomes 𝑓: 0.14 ( 20210 hom. )

Failed GnomAD Quality Control

Consequence

ADSS1
NM_001320424.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.20

Variant links:

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 links:

ADSS1 (HGNC:):

ADSS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014061332).

BP6

Variant 14-104729893-A-C is Benign according to our data. Variant chr14-104729893-A-C is described in ClinVar as [Benign]. Clinvar id is 769403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADSS1	NM_152328.5 linkuse as main transcript	c.193-5127A>C		intron_variant		ENST00000330877.7	NP_689541.1	Q8N142-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADSS1	ENST00000330877.7 linkuse as main transcript	c.193-5127A>C		intron_variant		1	NM_152328.5	ENSP00000331260.2		Q8N142-1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

27140

AN:

104892

Hom.:

6053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.323

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.570

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.308

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.260

GnomAD3 exomes

AF:

0.168

AC:

12407

AN:

73894

Hom.:

3309

AF XY:

0.163

AC XY:

6294

AN XY:

38730

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.0616

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.141

AC:

111525

AN:

789122

Hom.:

20210

Cov.:

AF XY:

0.151

AC XY:

59165

AN XY:

391196

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.300

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.259

AC:

27136

AN:

104930

Hom.:

6049

Cov.:

AF XY:

0.262

AC XY:

13218

AN XY:

50436

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.415

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.262

Alfa

AF:

0.0849

Hom.:

Bravo

AF:

0.311

TwinsUK

AF:

0.311

AC:

1153

ALSPAC

AF:

0.293

AC:

1130

ESP6500AA

AF:

0.211

AC:

863

ESP6500EA

AF:

0.299

AC:

2369

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

ADSS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 17, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

1.8

DANN

Benign

0.59

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.94

PROVEAN

Benign

0.10

REVEL

Benign

0.088

Sift

Benign

0.072

Sift4G

Benign

0.30

Polyphen

0.0030

Vest4

0.22

MutPred

0.94

Gain of catalytic residue at S5 (P = 6e-04);

ClinPred

0.0088

GERP RS

-0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over