chr1-244422841-T-G

Position:

• chr1-244422841-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001126.5(ADSS2):​c.657A>C​(p.Lys219Asn) 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: 32)
• Consequence: ADSS2 NM_001126.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.665

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2428565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADSS2	NM_001126.5	c.657A>C	p.Lys219Asn	missense_variant	7/13	ENST00000366535.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADSS2	ENST00000366535.4	c.657A>C	p.Lys219Asn	missense_variant	7/13	1	NM_001126.5	P1
ADSS2	ENST00000462358.1	n.778A>C		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.657A>C (p.K219N) alteration is located in exon 7 (coding exon 7) of the ADSS gene. This alteration results from a A to C substitution at nucleotide position 657, causing the lysine (K) at amino acid position 219 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Benign	0.064	T
Polyphen		0.066	B
Vest4		0.41
MutPred		0.54		Loss of ubiquitination at K219 (P = 0.0341);
MVP		0.36
MPC		0.79
ClinPred		0.93	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.81

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-244586143;