Genetic Variant ADSS1:p.Val2Val (chr14-104729898-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000332972.9(ADSS1):c.6G>T(p.Val2Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000846 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. Synonymous variant affecting the same amino acid position (i.e. V2V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000085 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADSS1
ENST00000332972.9 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

myopathy, distal, 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ADSS1 links:

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ACMG classification

Classification was made for transcript

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.00000847

AC:

AN:

118102

Hom.:

Cov.:

show subpopulations

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:

AN:

669904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

336650

African (AFR)

AF:

0.00

AC:

AN:

15030

American (AMR)

AF:

0.00

AC:

AN:

19418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15908

East Asian (EAS)

AF:

0.00

AC:

AN:

25312

South Asian (SAS)

AF:

0.00

AC:

AN:

45792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2558

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

482908

Other (OTH)

AF:

0.00

AC:

AN:

31276

GnomAD4 genome

AF:

0.00000846

AC:

AN:

118164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

56812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33624

American (AMR)

AF:

0.0000861

AC:

AN:

11620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2854

East Asian (EAS)

AF:

0.00

AC:

AN:

3408

South Asian (SAS)

AF:

0.00

AC:

AN:

3350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7538

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53264

Other (OTH)

AF:

0.00

AC:

AN:

1612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.44

PhyloP100

-0.14

PromoterAI

0.063

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over