17-10710861-C-G

Variant names:

• chr17-10710861-C-G
• NM_020233.5:c.746C>G

Variant summary

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

The NM_020233.5(ADPRM):​c.746C>G​(p.Ser249Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADPRM NM_020233.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• 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: 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=0.20727813).

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.746C>G	p.Ser249Cys	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.746C>G	p.Ser249Cys	missense	Exon 4 of 4	ENSP00000369099.4	Q3LIE5-1
	ADPRM	ENST00000468843.1	TSL:1	n.*216C>G		non_coding_transcript_exon	Exon 4 of 4	ENSP00000431622.1	Q3LIE5-3
	ADPRM	ENST00000468843.1	TSL:1	n.*216C>G		3_prime_UTR	Exon 4 of 4	ENSP00000431622.1	Q3LIE5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.10
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.96
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.21	T
PhyloP100		5.7
Sift4G	Benign	1.0	T
Vest4		0.23
MVP		0.21
ClinPred		0.73	D
GERP RS		4.8
Varity_R		0.097

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

hg19: chr17-10614178;