chr14-104729898-G-A

Variant names:

• chr14-104729898-G-A
• rs34672588
• ENST00000332972.9:c.6G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_199165.2(ADSS1):​c.6G>A​(p.Val2Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 787,880 control chromosomes in the GnomAD database, including 56,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (15282 hom., cov: 26)
  • Exomes 𝑓: 0.25 (41001 hom.)
• Consequence: ADSS1 NM_199165.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.145

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 14-104729898-G-A is Benign according to our data. Variant chr14-104729898-G-A is described in ClinVar as [Benign]. Clinvar id is 1189013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADSS1	NM_152328.5	c.193-5122G>A		intron_variant	Intron 1 of 12	ENST00000330877.7	NP_689541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADSS1	ENST00000330877.7	c.193-5122G>A		intron_variant	Intron 1 of 12	1	NM_152328.5	ENSP00000331260.2

Frequencies

GnomAD3 genomes AF: 0.458 AC: 54114 AN: 118048 Hom.: 15261 Cov.: 26

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.451

GnomAD2 exomes AF: 0.311 AC: 21025 AN: 67694 AF XY: 0.300

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.534

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.253 AC: 169475 AN: 669770 Hom.: 41001 Cov.: 17 AF XY: 0.266 AC XY: 89409 AN XY: 336586

Gnomad4 AFR exome AF: 0.398 AC: 5977 AN: 15020

Gnomad4 AMR exome AF: 0.393 AC: 7633 AN: 19408

Gnomad4 ASJ exome AF: 0.284 AC: 4523 AN: 15904

Gnomad4 EAS exome AF: 0.480 AC: 12154 AN: 25310

Gnomad4 SAS exome AF: 0.437 AC: 20021 AN: 45774

Gnomad4 FIN exome AF: 0.411 AC: 13039 AN: 31692

Gnomad4 NFE exome AF: 0.198 AC: 95503 AN: 482834

Gnomad4 Remaining exome AF: 0.316 AC: 9870 AN: 31270

GnomAD4 genome AF: 0.459 AC: 54155 AN: 118110 Hom.: 15282 Cov.: 26 AF XY: 0.461 AC XY: 26178 AN XY: 56788

Gnomad4 AFR AF: 0.529 AC: 0.52928 AN: 0.52928

Gnomad4 AMR AF: 0.482 AC: 0.481746 AN: 0.481746

Gnomad4 ASJ AF: 0.371 AC: 0.370617 AN: 0.370617

Gnomad4 EAS AF: 0.572 AC: 0.572225 AN: 0.572225

Gnomad4 SAS AF: 0.533 AC: 0.533453 AN: 0.533453

Gnomad4 FIN AF: 0.426 AC: 0.42567 AN: 0.42567

Gnomad4 NFE AF: 0.410 AC: 0.409624 AN: 0.409624

Gnomad4 OTH AF: 0.452 AC: 0.451613 AN: 0.451613

Alfa AF: 0.416 Hom.: 3562

Bravo AF: 0.492

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Myopathy, distal, 5 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.0
DANN	Benign	0.76
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34672588; hg19: chr14-105196235; COSMIC: COSV58271906;