1-220791529-C-G

Variant names:

• chr1-220791529-C-G
• NM_022746.4:c.314C>G
• MTARC1 p.Thr105Ser

Variant summary

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

The NM_022746.4(MTARC1):​c.314C>G​(p.Thr105Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.314C>G	p.Thr105Ser	missense	Exon 2 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.314C>G	p.Thr105Ser	missense	Exon 2 of 7	ENSP00000355877.5	Q5VT66-1
	ENSG00000286231	ENST00000651706.1		n.269C>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000499157.1	A0A494C1P3
	MTARC1	ENST00000694919.1		c.314C>G	p.Thr105Ser	missense	Exon 2 of 8	ENSP00000511594.1	A0A8Q3SHG3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.095	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Benign	0.069	T
Sift4G	Benign	0.17	T
PromoterAI		-0.099	Neutral
Varity_R		0.24
gMVP		0.64
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-220964871;