chr14-104729898-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001320424.1(ADSS1):​c.-722G>T 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 0.00000846 in 118,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000085 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADSS1 NM_001320424.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320424.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS1	NM_152328.5	MANE Select	c.193-5122G>T		intron	N/A	NP_689541.1	Q8N142-1
	ADSS1	NM_001320424.1		c.-722G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001307353.1	Q8N142
	ADSS1	NM_199165.2		c.6G>T	p.Val2Val	synonymous	Exon 1 of 13	NP_954634.1	B3KTV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS1	ENST00000332972.9	TSL:1	c.6G>T	p.Val2Val	synonymous	Exon 1 of 13	ENSP00000333019.5	Q8N142-2
	ADSS1	ENST00000330877.7	TSL:1 MANE Select	c.193-5122G>T		intron	N/A	ENSP00000331260.2	Q8N142-1
	ADSS1	ENST00000852145.1		c.193-5122G>T		intron	N/A	ENSP00000522204.1

Frequencies

GnomAD3 genomes AF: 0.00000847 AC: 1 AN: 118102 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000861

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 669904 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 336650

African (AFR) AF: 0.00 AC: 0 AN: 15030

American (AMR) AF: 0.00 AC: 0 AN: 19418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15908

East Asian (EAS) AF: 0.00 AC: 0 AN: 25312

South Asian (SAS) AF: 0.00 AC: 0 AN: 45792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 482908

Other (OTH) AF: 0.00 AC: 0 AN: 31276

GnomAD4 genome AF: 0.00000846 AC: 1 AN: 118164 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 56812

African (AFR) AF: 0.00 AC: 0 AN: 33624

American (AMR) AF: 0.0000861 AC: 1 AN: 11620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2854

East Asian (EAS) AF: 0.00 AC: 0 AN: 3408

South Asian (SAS) AF: 0.00 AC: 0 AN: 3350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53264

Other (OTH) AF: 0.00 AC: 0 AN: 1612

Alfa AF: 0.00 Hom.: 3562

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.3
DANN	Benign	0.44
PhyloP100		-0.14
PromoterAI		0.063	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs34672588; hg19: chr14-105196235;