NM_001351661.2:c.645+63573T>G

Variant names:

• chr20-15563420-T-G
• rs1011643
• NM_001351661.2:c.645+63573T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351661.2(MACROD2):​c.645+63573T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,072 control chromosomes in the GnomAD database, including 30,725 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (30725 hom., cov: 32)
• Consequence: MACROD2 NM_001351661.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• Publications: 3 publications found

Genes affected

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351661.2. 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
	MACROD2	NM_001351661.2	MANE Select	c.645+63573T>G		intron	N/A	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.645+63573T>G		intron	N/A	NP_001338592.1
	MACROD2	NM_080676.6		c.645+63573T>G		intron	N/A	NP_542407.2	A1Z1Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.645+63573T>G		intron	N/A	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000402914.5	TSL:1	c.-61+63573T>G		intron	N/A	ENSP00000385290.1	A1Z1Q3-4
	MACROD2	ENST00000642719.1		c.645+63573T>G		intron	N/A	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87298 AN: 151952 Hom.: 30727 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87301 AN: 152072 Hom.: 30725 Cov.: 32 AF XY: 0.569 AC XY: 42321 AN XY: 74334

African (AFR) AF: 0.155 AC: 6450 AN: 41492

American (AMR) AF: 0.598 AC: 9119 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2566 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3076 AN: 5164

South Asian (SAS) AF: 0.430 AC: 2071 AN: 4814

European-Finnish (FIN) AF: 0.737 AC: 7784 AN: 10562

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54115 AN: 68002

Other (OTH) AF: 0.608 AC: 1281 AN: 2108

Alfa AF: 0.690 Hom.: 16947

Bravo AF: 0.551

Asia WGS AF: 0.477 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.75
PhyloP100		-0.84
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: rs1011643; hg19: chr20-15544065;