Genetic Variant ENSG00000293000:n.1048C>A (chr8-85661992-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The ENST00000379010.3(ENSG00000293000):n.1048C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000012 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000293000
ENST00000379010.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.337

Publications

0 publications found

Variant links:

Genes affected

ENSG00000293000 (HGNC:):

ENSG00000293000 links:

REXO1L1P (HGNC:24660): (REXO1 like 1, pseudogene) Predicted to enable exonuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

REXO1L1P links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

BayesDel_noAF computational evidence supports a deleterious effect, 0.49

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379010.3. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293000	ENST00000379010.3	TSL:6	n.1048C>A		non_coding_transcript_exon	Exon 1 of 1
	REXO1L1P	ENST00000608646.2	TSL:6	n.1506C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

72692

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000123

AC:

AN:

406910

Hom.:

Cov.:

AF XY:

0.00000921

AC XY:

AN XY:

217184

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

8436

American (AMR)

AF:

0.00

AC:

AN:

17186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12156

East Asian (EAS)

AF:

0.000141

AC:

AN:

28270

South Asian (SAS)

AF:

0.0000228

AC:

AN:

43900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

246132

Other (OTH)

AF:

0.00

AC:

AN:

22672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.255

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

72694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33592

African (AFR)

AF:

0.00

AC:

AN:

9892

American (AMR)

AF:

0.00

AC:

AN:

7142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2366

East Asian (EAS)

AF:

0.00

AC:

AN:

3058

South Asian (SAS)

AF:

0.00

AC:

AN:

1912

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

41258

Other (OTH)

AF:

0.00

AC:

AN:

948

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Pathogenic

0.49

CADD

Benign

9.3

(source)

DANN

Uncertain

0.99

PhyloP100

0.34

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over