ENST00000332972.9:c.6G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000332972.9(ADSS1):​c.6G>C​(p.Val2Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V2V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: ADSS1 ENST00000332972.9 synonymous
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP7: Synonymous conserved (PhyloP=-0.145 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332972.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS1	ENST00000332972.9	TSL:1	c.6G>C	p.Val2Val	synonymous	Exon 1 of 13	ENSP00000333019.5
	ADSS1	ENST00000330877.7	TSL:1 MANE Select	c.193-5122G>C		intron	N/A	ENSP00000331260.2
	ADSS1	ENST00000553540.5	TSL:2	n.6G>C		non_coding_transcript_exon	Exon 1 of 13	ENSP00000450759.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 17

GnomAD4 genome Cov.: 26

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	4.1
DANN	Benign	0.35
PhyloP100		-0.14
PromoterAI		0.058	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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;