1-244411376-G-A

Variant names:

• chr1-244411376-G-A
• NM_001126.5:c.1229C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001126.5(ADSS2):​c.1229C>T​(p.Thr410Ile) variant causes a missense change. 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: 32)
• Consequence: ADSS2 NM_001126.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 0 publications found

Genes affected

ADSS2 (HGNC:292): (adenylosuccinate synthase 2) This gene encodes the enzyme adenylosuccinate synthetase which catalyzes the first committed step in the conversion of inosine monophosphate to adenosine monophosphate. A pseudogene of this gene is found on chromosome 17.[provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30666453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126.5. 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
	ADSS2	NM_001126.5	MANE Select	c.1229C>T	p.Thr410Ile	missense	Exon 12 of 13	NP_001117.2
	ADSS2	NM_001365073.2		c.1220C>T	p.Thr407Ile	missense	Exon 12 of 13	NP_001352002.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADSS2	ENST00000366535.4	TSL:1 MANE Select	c.1229C>T	p.Thr410Ile	missense	Exon 12 of 13	ENSP00000355493.3	P30520
	ADSS2	ENST00000468215.1	TSL:2	n.798C>T		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.17
Sift	Benign	0.031	D
Sift4G	Benign	0.084	T
Polyphen		0.69	P
Vest4		0.32
MutPred		0.52		Gain of catalytic residue at T410 (P = 0.256)
MVP		0.10
MPC		0.87
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.32
gMVP		0.82
Mutation Taster		=47/53	disease causing

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: chr1-244574678;