rs112720169

Variant names:

• chr17-10697803-C-T
• rs112720169
• NM_020233.5:c.-18+136C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020233.5(ADPRM):​c.-18+136C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00551 in 327,180 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (14 hom.)
• Consequence: ADPRM NM_020233.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.14
• 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]

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 Gene-Disease associations (from GenCC):

• mitochondrial complex IV deficiency, nuclear type 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-10697803-C-T is Benign according to our data. Variant chr17-10697803-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1223633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

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.-18+136C>T		intron	N/A	NP_064618.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPRM	ENST00000379774.5	TSL:1 MANE Select	c.-18+136C>T		intron	N/A	ENSP00000369099.4	Q3LIE5-1
	ADPRM	ENST00000468843.1	TSL:1	n.-18+136C>T		intron	N/A	ENSP00000431622.1	Q3LIE5-3
	ADPRM	ENST00000923982.1		c.-833C>T		5_prime_UTR	Exon 1 of 4	ENSP00000594041.1

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 1445 AN: 38090 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00143

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000930

Gnomad OTH AF: 0.0399

GnomAD4 exome AF: 0.00120 AC: 348 AN: 289048 Hom.: 14 Cov.: 3 AF XY: 0.00110 AC XY: 169 AN XY: 153028

African (AFR) AF: 0.0395 AC: 225 AN: 5702

American (AMR) AF: 0.00540 AC: 45 AN: 8328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8508

East Asian (EAS) AF: 0.00 AC: 0 AN: 16764

South Asian (SAS) AF: 0.000516 AC: 17 AN: 32944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20072

Middle Eastern (MID) AF: 0.000776 AC: 1 AN: 1288

European-Non Finnish (NFE) AF: 0.0000392 AC: 7 AN: 178432

Other (OTH) AF: 0.00312 AC: 53 AN: 17010

GnomAD4 genome AF: 0.0382 AC: 1455 AN: 38132 Hom.: 28 Cov.: 33 AF XY: 0.0395 AC XY: 717 AN XY: 18172

African (AFR) AF: 0.134 AC: 1342 AN: 10050

American (AMR) AF: 0.0238 AC: 77 AN: 3242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1260

East Asian (EAS) AF: 0.00 AC: 0 AN: 1118

South Asian (SAS) AF: 0.00144 AC: 1 AN: 694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 96

European-Non Finnish (NFE) AF: 0.000930 AC: 18 AN: 19346

Other (OTH) AF: 0.0395 AC: 17 AN: 430

Alfa AF: 0.00988 Hom.: 4

Bravo AF: 0.0114

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.69
DANN	Benign	0.84
PhyloP100		-2.1
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs112720169; hg19: chr17-10601120;