NM_020233.5:c.1022A>C

Variant names:

• chr17-10711137-A-C
• rs770073148
• NM_020233.5:c.1022A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020233.5(ADPRM):​c.1022A>C​(p.His341Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H341R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADPRM NM_020233.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056566983).

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.1022A>C	p.His341Pro	missense	Exon 4 of 4	NP_064618.3
	TMEM220	NM_001359647.2		c.*1248T>G		3_prime_UTR	Exon 6 of 6	NP_001346576.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRM	ENST00000379774.5	TSL:1 MANE Select	c.1022A>C	p.His341Pro	missense	Exon 4 of 4	ENSP00000369099.4	Q3LIE5-1
	ADPRM	ENST00000468843.1	TSL:1	n.*492A>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000431622.1	Q3LIE5-3
	ADPRM	ENST00000468843.1	TSL:1	n.*492A>C		3_prime_UTR	Exon 4 of 4	ENSP00000431622.1	Q3LIE5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448506 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718952

African (AFR) AF: 0.00 AC: 0 AN: 32910

American (AMR) AF: 0.00 AC: 0 AN: 43432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25766

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 85386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102992

Other (OTH) AF: 0.00 AC: 0 AN: 59758

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.29
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.064
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.10	B
Vest4		0.11
MutPred		0.24		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.040
MPC		0.61
ClinPred		0.097	T
GERP RS		-1.5
Varity_R		0.051
gMVP		0.72

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: rs770073148; hg19: chr17-10614454;