7-107563979-A-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_181581.3(DUS4L):c.-341A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DUS4L
NM_181581.3 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.232

Variant links:

Genes affected

DUS4L (HGNC:21517): (dihydrouridine synthase 4 like) Predicted to enable tRNA dihydrouridine synthase activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

DUS4L links:

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

COG5 links:

DUS4L-BCAP29 (HGNC:54422): (DUS4L-BCAP29 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring DUS4L (dihydrouridine synthase 4 like) and BCAP29 (B cell receptor associated protein 29) genes on chromosome 7. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2019]

DUS4L-BCAP29 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045625895).

BP6

Variant 7-107563979-A-C is Benign according to our data. Variant chr7-107563979-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206117.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-107563979-A-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUS4L	NM_181581.3 link	c.-341A>C		5_prime_UTR_variant	Exon 1 of 8	ENST00000265720.8	NP_853559.1	O95620-1A4D0R5
COG5	NM_006348.5 link	c.-83T>G		upstream_gene_variant		ENST00000297135.9	NP_006339.4	Q9UP83

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DUS4L	ENST00000265720 link	c.-341A>C	5_prime_UTR_variant	Exon 1 of 8	2	NM_181581.3	ENSP00000265720.3	O95620-1
DUS4L-BCAP29	ENST00000673757 link	c.-341A>C	5_prime_UTR_variant	Exon 1 of 15			ENSP00000501026.1	A0A669KAY5
COG5	ENST00000297135.9 link	c.-83T>G	upstream_gene_variant		1	NM_006348.5	ENSP00000297135.4	Q9UP83

Frequencies

GnomAD3 genomes

AF:

0.000306

AC:

AN:

140454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000239

Gnomad SAS

AF:

0.00126

Gnomad FIN

AF:

0.00153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000234

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

174986

AF XY:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00114

AC:

521

AN:

457192

Hom.:

Cov.:

AF XY:

0.000981

AC XY:

242

AN XY:

246802

show subpopulations

Gnomad4 AFR exome

AF:

0.000670

AC:

AN:

13438

Gnomad4 AMR exome

AF:

0.0000635

AC:

AN:

31516

Gnomad4 ASJ exome

AF:

0.000403

AC:

AN:

12412

Gnomad4 EAS exome

AF:

0.000436

AC:

AN:

13762

Gnomad4 SAS exome

AF:

0.000218

AC:

AN:

64198

Gnomad4 FIN exome

AF:

0.0000693

AC:

AN:

28868

Gnomad4 NFE exome

AF:

0.00171

AC:

464

AN:

271676

Gnomad4 Remaining exome

AF:

0.000912

AC:

AN:

19732

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

Heterozygous variant carriers

104

209

313

418

522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

104

130

<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: AS_VQSR

AF:

0.000299

AC:

AN:

140546

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

68224

show subpopulations

Gnomad4 AFR

AF:

0.000154

AC:

0.000153539

AN:

0.000153539

Gnomad4 AMR

AF:

0.000209

AC:

0.00020871

AN:

0.00020871

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000239

AC:

0.000238892

AN:

0.000238892

Gnomad4 SAS

AF:

0.00101

AC:

0.00100705

AN:

0.00100705

Gnomad4 FIN

AF:

0.00153

AC:

0.00153447

AN:

0.00153447

Gnomad4 NFE

AF:

0.000234

AC:

0.000234031

AN:

0.000234031

Gnomad4 OTH

AF:

0.00

AC:

AN:

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

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.1

DANN

Benign

0.80

DEOGEN2

Benign

0.0026

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.24

T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.28

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.17

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);

MVP

0.11

MPC

0.067

ClinPred

0.11

GERP RS

-1.6

Varity_R

0.052

gMVP

0.26

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

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