1-220796686-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022746.4(MTARC1):​c.493A>G​(p.Thr165Ala) variant causes a missense change. The variant allele was found at a frequency of 0.726 in 1,611,280 control chromosomes in the GnomAD database, including 426,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.78 (46648 hom., cov: 33)
  • Exomes 𝑓: 0.72 (380281 hom.)
• Consequence: MTARC1 NM_022746.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3516218E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTARC1	NM_022746.4	c.493A>G	p.Thr165Ala	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>G	p.Thr165Ala	missense_variant	Exon 3 of 7	1	NM_022746.4	ENSP00000355877.5
ENSG00000286231	ENST00000651706.1	n.448A>G		non_coding_transcript_exon_variant	Exon 3 of 9			ENSP00000499157.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118154 AN: 152082 Hom.: 46595 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.756

GnomAD3 exomes AF: 0.752 AC: 186349 AN: 247726 Hom.: 70727 AF XY: 0.745 AC XY: 99941 AN XY: 134074

Gnomad AFR exome AF: 0.924

Gnomad AMR exome AF: 0.827

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.793

Gnomad SAS exome AF: 0.774

Gnomad FIN exome AF: 0.716

Gnomad NFE exome AF: 0.708

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.720 AC: 1050848 AN: 1459080 Hom.: 380281 Cov.: 63 AF XY: 0.720 AC XY: 522454 AN XY: 725850

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.821

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.812

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.717

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.722

GnomAD4 genome AF: 0.777 AC: 118265 AN: 152200 Hom.: 46648 Cov.: 33 AF XY: 0.777 AC XY: 57834 AN XY: 74410

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.756

Alfa AF: 0.735 Hom.: 27581

Bravo AF: 0.794

TwinsUK AF: 0.710 AC: 2631

ALSPAC AF: 0.696 AC: 2681

ESP6500AA AF: 0.920 AC: 4053

ESP6500EA AF: 0.703 AC: 6048

ExAC AF: 0.754 AC: 91526

Asia WGS AF: 0.758 AC: 2639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.1
DANN	Benign	0.23
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0000024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.6	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.046
MPC		0.16
ClinPred		0.0059	T
GERP RS		3.9
Varity_R		0.038
gMVP		0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs2642438; hg19: chr1-220970028;