rs530058063

chr11-119180273-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_001282144.2(NLRX1):c.2252G>A(p.Arg751His) variant causes a missense change. The variant allele was found at a frequency of 0.0000215 in 1,581,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: NLRX1 NM_001282144.2 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.56

Genes affected

NLRX1 (HGNC:29890): (NLR family member X1) The protein encoded by this gene is a member of the NLR family and localizes to the outer mitochondrial membrane. The encoded protein is a regulator of mitochondrial antivirus responses. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05806747).
• BP6: Variant 11-119180273-G-A is Benign according to our data. Variant chr11-119180273-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 207861.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRX1	NM_001282144.2	c.2252G>A	p.Arg751His	missense_variant	7/10	ENST00000409109.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRX1	ENST00000409109.6	c.2252G>A	p.Arg751His	missense_variant	7/10	1	NM_001282144.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000520 AC: 12 AN: 230684 Hom.: 0 AF XY: 0.0000320 AC XY: 4 AN XY: 125030

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000663

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000161 AC: 23 AN: 1428886 Hom.: 0 Cov.: 32 AF XY: 0.00000993 AC XY: 7 AN XY: 705012

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000230

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000462

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000367

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74452

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	21
Dann	Benign	0.91
DEOGEN2	Benign	0.079	T;T;T;T;.
Eigen	Benign	0.085
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T;.;.;.;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.058	T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.69	N;N;N;N;N
MutationTaster	Benign	0.75	D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.56	N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.21	T;T;T;T;T
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.69	P;P;P;P;D
Vest4		0.39
MVP		0.72
MPC		0.91
ClinPred		0.19	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs530058063; hg19: chr11-119050982; COSMIC: COSV52706567; COSMIC: COSV52706567;