Genetic Variant DUS4L:c.-324A>G (chr7-107563996-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

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

The NM_181581.3(DUS4L):c.-324A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000641 in 1,248,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

DUS4L
NM_181581.3 5_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.92

Publications

0 publications found

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 (BayesDel_noAF=-0.96).

BP6

Variant 7-107563996-A-G is Benign according to our data. Variant chr7-107563996-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3048548.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181581.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DUS4L	NM_181581.3	MANE Select	c.-324A>G	5_prime_UTR	Exon 1 of 8	NP_853559.1	O95620-1
DUS4L-BCAP29	NM_001371364.2		c.-324A>G	5_prime_UTR	Exon 1 of 15	NP_001358293.1	A0A669KAY5
DUS4L-BCAP29	NM_001371365.2		c.-362A>G	5_prime_UTR	Exon 1 of 14	NP_001358294.1	A0A669KB27

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DUS4L	ENST00000265720.8	TSL:2 MANE Select	c.-324A>G	5_prime_UTR	Exon 1 of 8	ENSP00000265720.3	O95620-1
COG5	ENST00000347053.8	TSL:1	c.-100T>C	5_prime_UTR	Exon 1 of 21	ENSP00000334703.3	A0AAA9X096
COG5	ENST00000393603.7	TSL:1	c.-100T>C	5_prime_UTR	Exon 1 of 21	ENSP00000377228.3	A0AAA9X2X8

Frequencies

GnomAD3 genomes

AF:

0.0000427

AC:

AN:

140460

Hom.:

Cov.:

show subpopulations

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:

0.00159

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000127

AC:

AN:

156872

AF XY:

0.000163

show subpopulations

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

AF:

0.0000668

AC:

AN:

1107754

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

550120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25168

American (AMR)

AF:

0.00

AC:

AN:

31602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17532

East Asian (EAS)

AF:

0.00

AC:

AN:

18370

South Asian (SAS)

AF:

0.000938

AC:

AN:

75728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2920

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

863732

Other (OTH)

AF:

0.0000716

AC:

AN:

41874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.0000427

AC:

AN:

140568

Hom.:

Cov.:

AF XY:

0.0000587

AC XY:

AN XY:

68192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39370

American (AMR)

AF:

0.00

AC:

AN:

14380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3308

East Asian (EAS)

AF:

0.00

AC:

AN:

3950

South Asian (SAS)

AF:

0.00159

AC:

AN:

3784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64010

Other (OTH)

AF:

0.00

AC:

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

COG5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.058

(source)

DANN

Benign

0.47

PhyloP100

-4.9

PromoterAI

-0.037

Neutral

(source)

Mutation Taster

=295/5

polymorphism

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over