chr11-63998997-C-G

Variant names:

• chr11-63998997-C-G
• rs111575182
• NM_014067.4:c.931G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014067.4(MACROD1):​c.931G>C​(p.Glu311Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MACROD1 NM_014067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

Genes affected

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

OTUB1 (HGNC:23077): (OTU deubiquitinase, ubiquitin aldehyde binding 1) The product of this gene is a member of the OTU (ovarian tumor) superfamily of predicted cysteine proteases. The encoded protein is a highly specific ubiquitin iso-peptidase, and cleaves ubiquitin from branched poly-ubiquitin chains but not from ubiquitinated substrates. It interacts with another ubiquitin protease and an E3 ubiquitin ligase that inhibits cytokine gene transcription in the immune system. It is proposed to function in specific ubiquitin-dependent pathways, possibly by providing an editing function for polyubiquitin chain growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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=0.09705889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MACROD1	NM_014067.4	c.931G>C	p.Glu311Gln	missense_variant	Exon 9 of 11	ENST00000255681.7	NP_054786.2
MACROD1	NM_001411019.1	c.931G>C	p.Glu311Gln	missense_variant	Exon 9 of 10		NP_001397948.1
MACROD1	XM_011544970.3	c.901G>C	p.Glu301Gln	missense_variant	Exon 8 of 9		XP_011543272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MACROD1	ENST00000255681.7	c.931G>C	p.Glu311Gln	missense_variant	Exon 9 of 11	1	NM_014067.4	ENSP00000255681.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.026
Sift	Benign	0.31	T
Sift4G	Benign	0.46	T
Polyphen		0.099	B
Vest4		0.35
MutPred		0.42		Loss of phosphorylation at S316 (P = 0.1402);
MVP		0.12
MPC		0.26
ClinPred		0.20	T
GERP RS		3.6
Varity_R		0.28
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs111575182; hg19: chr11-63766469;