17-10705166-T-A

Variant names:

• chr17-10705166-T-A
• NM_020233.5:c.240T>A

Variant summary

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

The NM_020233.5(ADPRM):​c.240T>A​(p.Asn80Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADPRM NM_020233.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.236

Genes affected

ADPRM (HGNC:30925): (ADP-ribose/CDP-alcohol diphosphatase, manganese dependent) Predicted to enable 2',3'-cyclic-nucleotide 2'-phosphodiesterase activity; manganese ion binding activity; and pyrophosphatase activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TMEM220 (HGNC:33757): (transmembrane protein 220) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADPRM	NM_020233.5	c.240T>A	p.Asn80Lys	missense_variant	Exon 2 of 4	ENST00000379774.5	NP_064618.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADPRM	ENST00000379774.5	c.240T>A	p.Asn80Lys	missense_variant	Exon 2 of 4	1	NM_020233.5	ENSP00000369099.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.240T>A (p.N80K) alteration is located in exon 2 (coding exon 1) of the ADPRM gene. This alteration results from a T to A substitution at nucleotide position 240, causing the asparagine (N) at amino acid position 80 to be replaced by a lysine (K). 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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.2	D;.
REVEL	Uncertain	0.58
Sift	Benign	0.28	T;.
Sift4G	Benign	0.32	T;T
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.57		Gain of ubiquitination at N80 (P = 0.0267);Gain of ubiquitination at N80 (P = 0.0267);
MVP		0.53
MPC		1.2
ClinPred		0.84	D
GERP RS		-2.7
Varity_R		0.29
gMVP		0.87

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: chr17-10608483;