1-220786955-C-G

Variant names:

• chr1-220786955-C-G
• rs1032723356
• NM_022746.4:c.11C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022746.4(MTARC1):​c.11C>G​(p.Ala4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

MTARC1 (HGNC:26189): (mitochondrial amidoxime reducing component 1) Enables molybdenum ion binding activity; molybdopterin cofactor binding activity; and oxidoreductase activity, acting on other nitrogenous compounds as donors. Contributes to nitrite reductase (NO-forming) activity. Involved in cellular detoxification of nitrogen compound; nitrate metabolic process; and nitric oxide biosynthetic process. Located in mitochondrion. Part of nitric-oxide synthase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286231 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07108644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022746.4. 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
	MTARC1	NM_022746.4	MANE Select	c.11C>G	p.Ala4Gly	missense	Exon 1 of 7	NP_073583.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTARC1	ENST00000366910.10	TSL:1 MANE Select	c.11C>G	p.Ala4Gly	missense	Exon 1 of 7	ENSP00000355877.5	Q5VT66-1
	MTARC1	ENST00000694919.1		c.11C>G	p.Ala4Gly	missense	Exon 1 of 8	ENSP00000511594.1	A0A8Q3SHG3
	MTARC1	ENST00000865600.1		c.11C>G	p.Ala4Gly	missense	Exon 1 of 6	ENSP00000535659.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1089860 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 517978

African (AFR) AF: 0.0000443 AC: 1 AN: 22568

American (AMR) AF: 0.00 AC: 0 AN: 8112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14000

East Asian (EAS) AF: 0.00 AC: 0 AN: 25974

South Asian (SAS) AF: 0.00 AC: 0 AN: 21844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2928

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 927576

Other (OTH) AF: 0.00 AC: 0 AN: 43636

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.043
Sift	Uncertain	0.026	D
Sift4G	Benign	0.092	T
Polyphen		0.025	B
Vest4		0.13
MutPred		0.15		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.092
MPC		0.17
ClinPred		0.19	T
GERP RS		2.9
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.12
gMVP		0.28
Mutation Taster		=95/5	polymorphism

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: rs1032723356; hg19: chr1-220960297;