rs199523732

Variant names:

• chr17-10710857-G-A
• rs199523732
• NM_020233.5:c.742G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-10710857-G-A
• chr17-10710857-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020233.5(ADPRM):​c.742G>A​(p.Ala248Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,613,686 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: ADPRM NM_020233.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.596
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13761407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020233.5. 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
	ADPRM	NM_020233.5	MANE Select	c.742G>A	p.Ala248Thr	missense	Exon 4 of 4	NP_064618.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRM	ENST00000379774.5	TSL:1 MANE Select	c.742G>A	p.Ala248Thr	missense	Exon 4 of 4	ENSP00000369099.4	Q3LIE5-1
	ADPRM	ENST00000468843.1	TSL:1	n.*212G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000431622.1	Q3LIE5-3
	ADPRM	ENST00000468843.1	TSL:1	n.*212G>A		3_prime_UTR	Exon 4 of 4	ENSP00000431622.1	Q3LIE5-3

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 151996 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000243 AC: 61 AN: 250984 AF XY: 0.000243

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000397

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000453 AC: 662 AN: 1461690 Hom.: 1 Cov.: 31 AF XY: 0.000415 AC XY: 302 AN XY: 727150

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86230

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000556 AC: 618 AN: 1111858

Other (OTH) AF: 0.000331 AC: 20 AN: 60388

GnomAD4 genome AF: 0.000368 AC: 56 AN: 151996 Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17 AN XY: 74244

African (AFR) AF: 0.000169 AC: 7 AN: 41372

American (AMR) AF: 0.000131 AC: 2 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68002

Other (OTH) AF: 0.000958 AC: 2 AN: 2088

Alfa AF: 0.000452 Hom.: 0

Bravo AF: 0.000302

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000264 AC: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000474

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	-0.31	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	0.0071	D
MutationAssessor	Benign	1.3	L
PhyloP100		0.60
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.39
Sift	Benign	0.10	T
Sift4G	Uncertain	0.060	T
Polyphen		1.0	D
Vest4		0.045
MVP		0.56
MPC		0.82
ClinPred		0.075	T
GERP RS		0.43
Varity_R		0.035
gMVP		0.42
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

dbSNP: rs199523732; hg19: chr17-10614174; COSMIC: COSV59379813; COSMIC: COSV59379813;