6-143428491-A-C

Variant names:

• chr6-143428491-A-C
• rs756656977
• NM_182503.3:c.548T>G

Variant summary

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

The NM_182503.3(ADAT2):​c.548T>G​(p.Val183Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000014 (0 hom.)
• Consequence: ADAT2 NM_182503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

Genes affected

ADAT2 (HGNC:21172): (adenosine deaminase tRNA specific 2) Predicted to enable tRNA-specific adenosine-34 deaminase activity. Predicted to be involved in tRNA wobble adenosine to inosine editing. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.17772388).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182503.3. 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
	ADAT2	NM_182503.3	MANE Select	c.548T>G	p.Val183Gly	missense	Exon 6 of 6	NP_872309.2	Q7Z6V5-1
	ADAT2	NM_001286259.2		c.407T>G	p.Val136Gly	missense	Exon 6 of 6	NP_001273188.1	Q7Z6V5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAT2	ENST00000237283.9	TSL:1 MANE Select	c.548T>G	p.Val183Gly	missense	Exon 6 of 6	ENSP00000237283.8	Q7Z6V5-1
	ADAT2	ENST00000606514.5	TSL:1	c.407T>G	p.Val136Gly	missense	Exon 6 of 6	ENSP00000475651.1	Q7Z6V5-2
	ADAT2	ENST00000933835.1		c.443T>G	p.Val148Gly	missense	Exon 5 of 5	ENSP00000603894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249346 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461654 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000828 AC: 1

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	0.23
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.062
Sift	Benign	0.39	T
Sift4G	Benign	0.38	T
Polyphen		0.87	P
Vest4		0.34
MutPred		0.26		Loss of stability (P = 0.0075)
MVP		0.73
MPC		0.60
ClinPred		0.44	T
GERP RS		5.5
Varity_R		0.24
gMVP		0.29
Mutation Taster		=82/18	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

dbSNP: rs756656977; hg19: chr6-143749628;