Genetic Variant ADPRM:c.-31G>A (chr17-10697654-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020233.5(ADPRM):c.-31G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,006,200 control chromosomes in the GnomAD database, including 843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 523 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 320 hom. )

Consequence

ADPRM
NM_020233.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.160

Variant links:

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]

ADPRM links:

SCO1 (HGNC:10603): (synthesis of cytochrome C oxidase 1) Mammalian cytochrome c oxidase (COX) catalyzes the transfer of reducing equivalents from cytochrome c to molecular oxygen and pumps protons across the inner mitochondrial membrane. In yeast, 2 related COX assembly genes, SCO1 and SCO2 (synthesis of cytochrome c oxidase), enable subunits 1 and 2 to be incorporated into the holoprotein. This gene is the human homolog to the yeast SCO1 gene. [provided by RefSeq, Jul 2008]

SCO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-10697654-G-A is Benign according to our data. Variant chr17-10697654-G-A is described in ClinVar as [Benign]. Clinvar id is 1240455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADPRM	NM_020233.5 link	c.-31G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000379774.5	NP_064618.3	Q3LIE5-1W0NWJ0
SCO1	NM_004589.4 link	c.-147C>T		upstream_gene_variant		ENST00000255390.10	NP_004580.1	O75880

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADPRM	ENST00000379774 link	c.-31G>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_020233.5	ENSP00000369099.4		Q3LIE5-1
SCO1	ENST00000255390.10 link	c.-147C>T		upstream_gene_variant		1	NM_004589.4	ENSP00000255390.5		O75880

Frequencies

GnomAD3 genomes

AF:

0.0454

AC:

6912

AN:

152240

Hom.:

518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.0387

GnomAD4 exome

AF:

0.00589

AC:

5033

AN:

853844

Hom.:

320

Cov.:

AF XY:

0.00504

AC XY:

2214

AN XY:

439584

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.000511

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000827

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000614

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0456

AC:

6944

AN:

152356

Hom.:

523

Cov.:

AF XY:

0.0445

AC XY:

3318

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.0238

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0541

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.0

DANN

Benign

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over