Genetic Variant DIS3L:p.His280His (chr15-66315061-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001323940.2(DIS3L):c.-101C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

DIS3L
NM_001323940.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.12

Publications

0 publications found

Variant links:

Genes affected

DIS3L (HGNC:28698): (DIS3 like exosome 3'-5' exoribonuclease) The cytoplasmic RNA exosome complex degrades unstable mRNAs and is involved in the regular turnover of other mRNAs. The protein encoded by this gene contains 3'-5' exoribonuclease activity and is a catalytic component of this complex. [provided by RefSeq, May 2016]

DIS3L links:

ENSG00000260773 (HGNC:):

ENSG00000260773 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323940.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIS3L	NM_001143688.3	MANE Select	c.840C>T	p.His280His	synonymous	Exon 7 of 17	NP_001137160.1	Q8TF46-1
DIS3L	NM_001323940.2		c.-101C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 16	NP_001310869.1
DIS3L	NM_001323943.2		c.-101C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 16	NP_001310872.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DIS3L	ENST00000319212.9	TSL:5 MANE Select	c.840C>T	p.His280His	synonymous	Exon 7 of 17	ENSP00000321711.4	Q8TF46-1
DIS3L	ENST00000319194.9	TSL:1	c.591C>T	p.His197His	synonymous	Exon 7 of 17	ENSP00000321583.5	Q8TF46-4
DIS3L	ENST00000530537.1	TSL:1	n.*350C>T		non_coding_transcript_exon	Exon 6 of 16	ENSP00000432407.1	E9PKI7

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

251166

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000725

AC:

106

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000671

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000845

AC:

AN:

1111900

Other (OTH)

AF:

0.0000994

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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

AF:

0.0000789

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.24

(source)

DANN

Benign

0.79

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over