Genetic Variant NM_152328.5:c.97G>A (chr14-104724367-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152328.5(ADSS1):c.97G>A(p.Val33Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000024 in 1,251,242 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V33L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

ADSS1
NM_152328.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.98

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152328.5. 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.97G>A	p.Val33Met	missense	Exon 1 of 13	NP_689541.1	Q8N142-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADSS1	ENST00000330877.7	TSL:1 MANE Select	c.97G>A	p.Val33Met	missense	Exon 1 of 13	ENSP00000331260.2	Q8N142-1
ADSS1	ENST00000852145.1		c.97G>A	p.Val33Met	missense	Exon 1 of 13	ENSP00000522204.1
ADSS1	ENST00000710323.1		c.97G>A	p.Val33Met	missense	Exon 1 of 13	ENSP00000518203.1	Q8N142-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.10e-7

AC:

AN:

1099080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

520214

show subpopulations

African (AFR)

AF:

0.0000423

AC:

AN:

23624

American (AMR)

AF:

0.00

AC:

AN:

9196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14386

East Asian (EAS)

AF:

0.00

AC:

AN:

27352

South Asian (SAS)

AF:

0.00

AC:

AN:

20296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2968

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

924770

Other (OTH)

AF:

0.00

AC:

AN:

44042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000108

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

0.00075

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.84

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.7

PhyloP100

6.0

PROVEAN

Benign

-2.1

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.42

MutPred

0.52

Gain of MoRF binding (P = 0.0911)

MVP

0.62

ClinPred

0.96

GERP RS

2.9

PromoterAI

-0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.26

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over