rs6644

Variant names:

• chr14-104747006-A-G
• rs6644
• NM_152328.5:c.*3A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.73
• Publications: 29 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 -20 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 VariationId is 1189017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ADSS1	NM_152328.5	c.*3A>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000330877.7	NP_689541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADSS1	ENST00000330877.7	c.*3A>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_152328.5	ENSP00000331260.2

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

GnomAD2 exomes AF: 0.547 AC: 137562 AN: 251342 AF XY: 0.534

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 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

African (AFR) AF: 0.908 AC: 30378 AN: 33466

American (AMR) AF: 0.678 AC: 30301 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 10781 AN: 26090

East Asian (EAS) AF: 0.583 AC: 23110 AN: 39662

South Asian (SAS) AF: 0.574 AC: 49499 AN: 86178

European-Finnish (FIN) AF: 0.500 AC: 26698 AN: 53380

Middle Eastern (MID) AF: 0.505 AC: 2912 AN: 5766

European-Non Finnish (NFE) AF: 0.450 AC: 499455 AN: 1110954

Other (OTH) AF: 0.508 AC: 30645 AN: 60346

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

African (AFR) AF: 0.889 AC: 36921 AN: 41538

American (AMR) AF: 0.634 AC: 9692 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3468

East Asian (EAS) AF: 0.632 AC: 3269 AN: 5176

South Asian (SAS) AF: 0.612 AC: 2954 AN: 4824

European-Finnish (FIN) AF: 0.498 AC: 5269 AN: 10572

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31137 AN: 67960

Other (OTH) AF: 0.584 AC: 1235 AN: 2116

Alfa AF: 0.516 Hom.: 38079

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Myopathy, distal, 5 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.34
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: rs6644; hg19: chr14-105213343; COSMIC: COSV58273773; COSMIC: COSV58273773;