chrX-118975165-G-A

Variant names:

• chrX-118975165-G-A
• rs776496199
• NM_001031855.3:c.385G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001031855.3(LONRF3):​c.385G>A​(p.Gly129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,173,696 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000032 (0 hom. 21 hem.)
• Consequence: LONRF3 NM_001031855.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.214
• Publications: 1 publications found

Genes affected

LONRF3 (HGNC:21152): (LON peptidase N-terminal domain and ring finger 3) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Multiple alternatively spliced transcript variants have been suggested, but their full length natures are not clear. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033291608).
• BP6: Variant X-118975165-G-A is Benign according to our data. Variant chrX-118975165-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3867676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 21 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031855.3. 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
	LONRF3	NM_001031855.3	MANE Select	c.385G>A	p.Gly129Ser	missense	Exon 1 of 11	NP_001027026.1	Q496Y0-1
	LONRF3	NM_024778.5		c.385G>A	p.Gly129Ser	missense	Exon 1 of 10	NP_079054.3	A8K2D3
	LONRF3	NR_110311.1		n.552G>A		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONRF3	ENST00000371628.8	TSL:1 MANE Select	c.385G>A	p.Gly129Ser	missense	Exon 1 of 11	ENSP00000360690.3	Q496Y0-1
	LONRF3	ENST00000304778.11	TSL:1	c.385G>A	p.Gly129Ser	missense	Exon 1 of 10	ENSP00000307732.7	Q496Y0-2
	LONRF3	ENST00000961937.1		c.385G>A	p.Gly129Ser	missense	Exon 1 of 10	ENSP00000631996.1

Frequencies

GnomAD3 genomes AF: 0.00000884 AC: 1 AN: 113105 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000357

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000178 AC: 2 AN: 112122 AF XY: 0.0000262

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000321 AC: 34 AN: 1060546 Hom.: 0 Cov.: 34 AF XY: 0.0000607 AC XY: 21 AN XY: 346088

African (AFR) AF: 0.00 AC: 0 AN: 25269

American (AMR) AF: 0.00 AC: 0 AN: 28852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18752

East Asian (EAS) AF: 0.00 AC: 0 AN: 27800

South Asian (SAS) AF: 0.000494 AC: 25 AN: 50591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3534

European-Non Finnish (NFE) AF: 0.00000728 AC: 6 AN: 824135

Other (OTH) AF: 0.0000672 AC: 3 AN: 44617

GnomAD4 genome AF: 0.00000884 AC: 1 AN: 113150 Hom.: 0 Cov.: 24 AF XY: 0.0000283 AC XY: 1 AN XY: 35316

African (AFR) AF: 0.00 AC: 0 AN: 31276

American (AMR) AF: 0.00 AC: 0 AN: 10928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.000358 AC: 1 AN: 2796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6301

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53203

Other (OTH) AF: 0.00 AC: 0 AN: 1553

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000482 AC: 5

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.1
DANN	Benign	0.82
DEOGEN2	Benign	0.0072	T
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.14	N
PhyloP100		0.21
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.13
Sift	Benign	0.74	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.25		Gain of glycosylation at G129 (P = 0.0066)
MVP		0.52
MPC		0.38
ClinPred		0.021	T
GERP RS		1.2
PromoterAI		0.0054	Neutral
Varity_R		0.036
gMVP		0.27
Mutation Taster		=98/2	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: rs776496199; hg19: chrX-118109128; COSMIC: COSV100504795; COSMIC: COSV100504795;