chr14-104724362-C-A

Variant names:

• chr14-104724362-C-A
• NM_152328.5:c.92C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152328.5(ADSS1):​c.92C>A​(p.Ser31Tyr) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADSS1 NM_152328.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.166
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19362128).

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.92C>A	p.Ser31Tyr	missense	Exon 1 of 13	NP_689541.1	Q8N142-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS1	ENST00000330877.7	TSL:1 MANE Select	c.92C>A	p.Ser31Tyr	missense	Exon 1 of 13	ENSP00000331260.2	Q8N142-1
	ADSS1	ENST00000852145.1		c.92C>A	p.Ser31Tyr	missense	Exon 1 of 13	ENSP00000522204.1
	ADSS1	ENST00000710323.1		c.92C>A	p.Ser31Tyr	missense	Exon 1 of 13	ENSP00000518203.1	Q8N142-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1096856 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 519078

African (AFR) AF: 0.00 AC: 0 AN: 23502

American (AMR) AF: 0.00 AC: 0 AN: 8948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14376

East Asian (EAS) AF: 0.00 AC: 0 AN: 27220

South Asian (SAS) AF: 0.00 AC: 0 AN: 20136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2962

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923734

Other (OTH) AF: 0.00 AC: 0 AN: 43950

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.021
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.078
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.88	P
Vest4		0.24
MutPred		0.34		Loss of disorder (P = 0.0116)
MVP		0.75
ClinPred		0.48	T
GERP RS		2.8
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

hg19: chr14-105190699;