17-10710861-C-G

Position:

• chr17-10710861-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 9/14 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

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20727813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADPRM	NM_020233.5	c.746C>G	p.Ser249Cys	missense_variant	4/4	ENST00000379774.5	NP_064618.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADPRM	ENST00000379774.5	c.746C>G	p.Ser249Cys	missense_variant	4/4	1	NM_020233.5	ENSP00000369099.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.746C>G (p.S249C) alteration is located in exon 4 (coding exon 3) of the ADPRM gene. This alteration results from a C to G substitution at nucleotide position 746, causing the serine (S) at amino acid position 249 to be replaced by a cysteine (C). 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	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
Sift4G	Benign	1.0	T
Vest4		0.23
MVP		0.21
ClinPred		0.73	D
GERP RS		4.8

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: chr17-10614178;