Variant 3-142329608-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001282857.2(XRN1):c.4230T>C(p.Tyr1410=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00925 in 1,534,790 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 4 hom., cov: 31)

Exomes 𝑓: 0.0096 ( 72 hom. )

Consequence

XRN1
NM_001282857.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0120

Variant links:

Genes affected

XRN1 (HGNC:30654): (5'-3' exoribonuclease 1) This gene encodes a member of the 5'-3' exonuclease family. The encoded protein may be involved in replication-dependent histone mRNA degradation, and interacts directly with the enhancer of mRNA-decapping protein 4. In addition to mRNA metabolism, a similar protein in yeast has been implicated in a variety of nuclear and cytoplasmic functions, including homologous recombination, meiosis, telomere maintenance, and microtubule assembly. Mutations in this gene are associated with osteosarcoma, suggesting that the encoded protein may also play a role in bone formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

XRN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-142329608-A-G is Benign according to our data. Variant chr3-142329608-A-G is described in ClinVar as [Benign]. Clinvar id is 717836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.012 with no splicing effect.

BS2

High AC in GnomAd4 at 981 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRN1	NM_001282857.2 linkuse as main transcript	c.4230T>C	p.Tyr1410=	synonymous_variant	37/41	ENST00000392981.7	NP_001269786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRN1	ENST00000392981.7 linkuse as main transcript	c.4230T>C	p.Tyr1410=	synonymous_variant	37/41	1	NM_001282857.2	ENSP00000376707	P3	Q8IZH2-2

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

982

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00935

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00941

AC:

1690

AN:

179586

Hom.:

AF XY:

0.00898

AC XY:

889

AN XY:

98992

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00181

Gnomad ASJ exome

AF:

0.0317

Gnomad EAS exome

AF:

0.000943

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00956

AC:

13212

AN:

1382454

Hom.:

Cov.:

AF XY:

0.00926

AC XY:

6350

AN XY:

685542

show subpopulations

Gnomad4 AFR exome

AF:

0.000931

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.0340

Gnomad4 EAS exome

AF:

0.000471

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00875

GnomAD4 genome

AF:

0.00644

AC:

981

AN:

152336

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.00935

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00603

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

DANN

Benign

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over