NM_001351661.2:c.-6G>A

Variant names:

• chr20-13995758-G-A
• rs200598669
• NM_001351661.2:c.-6G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001351661.2(MACROD2):​c.-6G>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 0.000593 in 1,376,724 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: MACROD2 NM_001351661.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.46
• Publications: 0 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]

SEL1L2 (HGNC:15897): (SEL1L2 adaptor subunit of SYVN1 ubiquitin ligase) Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be part of Hrd1p ubiquitin ligase ERAD-L complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 20-13995758-G-A is Benign according to our data. Variant chr20-13995758-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3038275.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-6G>A		5_prime_UTR	Exon 1 of 18	NP_001338590.1	A1Z1Q3-1
	MACROD2	NM_001351663.2		c.-6G>A		5_prime_UTR	Exon 1 of 18	NP_001338592.1
	MACROD2	NM_080676.6		c.-6G>A		5_prime_UTR	Exon 1 of 17	NP_542407.2	A1Z1Q3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MACROD2	ENST00000684519.1	MANE Select	c.-6G>A		5_prime_UTR	Exon 1 of 18	ENSP00000507484.1	A1Z1Q3-1
	MACROD2	ENST00000483997.5	TSL:1	n.257G>A		non_coding_transcript_exon	Exon 1 of 4
	MACROD2	ENST00000642719.1		c.-6G>A		5_prime_UTR	Exon 1 of 18	ENSP00000496601.1	A0A2R8YFN3

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 434 AN: 143584 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00179

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000306

Gnomad OTH AF: 0.00196

GnomAD2 exomes AF: 0.000728 AC: 181 AN: 248568 AF XY: 0.000595

Gnomad AFR exome AF: 0.00989

Gnomad AMR exome AF: 0.000551

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000309 AC: 381 AN: 1232988 Hom.: 1 Cov.: 36 AF XY: 0.000293 AC XY: 179 AN XY: 611130

African (AFR) AF: 0.0110 AC: 296 AN: 26834

American (AMR) AF: 0.000876 AC: 33 AN: 37690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17500

East Asian (EAS) AF: 0.00 AC: 0 AN: 18632

South Asian (SAS) AF: 0.0000358 AC: 3 AN: 83868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4554

European-Non Finnish (NFE) AF: 0.0000176 AC: 17 AN: 965170

Other (OTH) AF: 0.000708 AC: 32 AN: 45168

GnomAD4 genome AF: 0.00303 AC: 435 AN: 143736 Hom.: 0 Cov.: 32 AF XY: 0.00299 AC XY: 209 AN XY: 69932

African (AFR) AF: 0.0101 AC: 403 AN: 40098

American (AMR) AF: 0.00178 AC: 26 AN: 14588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3346

East Asian (EAS) AF: 0.00 AC: 0 AN: 4126

South Asian (SAS) AF: 0.00 AC: 0 AN: 3918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000306 AC: 2 AN: 65276

Other (OTH) AF: 0.00194 AC: 4 AN: 2060

Alfa AF: 0.00108 Hom.: 1

Bravo AF: 0.00337

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MACROD2-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		2.5
PromoterAI		-0.025	Neutral
Mutation Taster		=286/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200598669; hg19: chr20-13976404;