chrX-118974819-C-T

Variant names:

• chrX-118974819-C-T
• rs376688770
• NM_001031855.3:c.39C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001031855.3(LONRF3):​c.39C>T​(p.Pro13Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,206,837 control chromosomes in the GnomAD database, including 1 homozygotes. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000073 (1 hom. 22 hem.)
• Consequence: LONRF3 NM_001031855.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.169
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant X-118974819-C-T is Benign according to our data. Variant chrX-118974819-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.169 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 22 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.39C>T	p.Pro13Pro	synonymous	Exon 1 of 11	NP_001027026.1	Q496Y0-1
	LONRF3	NM_024778.5		c.39C>T	p.Pro13Pro	synonymous	Exon 1 of 10	NP_079054.3	A8K2D3
	LONRF3	NR_110311.1		n.206C>T		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.39C>T	p.Pro13Pro	synonymous	Exon 1 of 11	ENSP00000360690.3	Q496Y0-1
	LONRF3	ENST00000304778.11	TSL:1	c.39C>T	p.Pro13Pro	synonymous	Exon 1 of 10	ENSP00000307732.7	Q496Y0-2
	LONRF3	ENST00000961937.1		c.39C>T	p.Pro13Pro	synonymous	Exon 1 of 10	ENSP00000631996.1

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112435 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000473 AC: 8 AN: 169044 AF XY: 0.0000514

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000731 AC: 80 AN: 1094402 Hom.: 1 Cov.: 29 AF XY: 0.0000610 AC XY: 22 AN XY: 360672

African (AFR) AF: 0.0000379 AC: 1 AN: 26364

American (AMR) AF: 0.0000287 AC: 1 AN: 34888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19314

East Asian (EAS) AF: 0.00 AC: 0 AN: 30056

South Asian (SAS) AF: 0.00 AC: 0 AN: 53438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39307

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.0000868 AC: 73 AN: 840966

Other (OTH) AF: 0.000109 AC: 5 AN: 45942

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112435 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34591

African (AFR) AF: 0.0000645 AC: 2 AN: 30999

American (AMR) AF: 0.00 AC: 0 AN: 10754

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3531

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6213

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53159

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.17
PromoterAI		-0.018	Neutral
Mutation Taster		=99/1	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: rs376688770; hg19: chrX-118108782;