1-220796686-A-T

Variant names:

• chr1-220796686-A-T
• rs2642438
• NM_022746.4:c.493A>T

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.493A>T​(p.Thr165Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91
• Publications: 153 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=0.17480701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC1	NM_022746.4	c.493A>T	p.Thr165Ser	missense_variant	Exon 3 of 7	ENST00000366910.10	NP_073583.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTARC1	ENST00000366910.10	c.493A>T	p.Thr165Ser	missense_variant	Exon 3 of 7	1	NM_022746.4	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1	n.448A>T		non_coding_transcript_exon_variant	Exon 3 of 9			ENSP00000499157.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459156 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 725884

African (AFR) AF: 0.00 AC: 0 AN: 33296

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39414

South Asian (SAS) AF: 0.00 AC: 0 AN: 85702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110950

Other (OTH) AF: 0.00 AC: 0 AN: 60298

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.099
Sift	Benign	0.066	T
Sift4G	Uncertain	0.020	D
Polyphen		0.0030	B
Vest4		0.12
MutPred		0.59		Gain of catalytic residue at T165 (P = 0.0814);
MVP		0.18
MPC		0.15
ClinPred		0.32	T
GERP RS		3.9
PromoterAI		0.096	Neutral
Varity_R		0.047
gMVP		0.32
Mutation Taster		=91/9	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: rs2642438; hg19: chr1-220970028;