7-107563995-C-T

Position:

chr7-107563995-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_181581.3(DUS4L):c.-325C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,561,280 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 40 hom. )

Consequence

DUS4L
NM_181581.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.825

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:):

DUS4L-BCAP29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-107563995-C-T is Benign according to our data. Variant chr7-107563995-C-T is described in ClinVar as [Benign]. Clinvar id is 358480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2083/152268) while in subpopulation AFR AF= 0.0468 (1945/41562). AF 95% confidence interval is 0.0451. There are 55 homozygotes in gnomad4. There are 953 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUS4L	NM_181581.3 linkuse as main transcript	c.-325C>T		5_prime_UTR_variant	1/8	ENST00000265720.8
DUS4L-BCAP29	NR_163940.2 linkuse as main transcript	n.25C>T		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUS4L	ENST00000265720.8 linkuse as main transcript	c.-325C>T		5_prime_UTR_variant	1/8	2	NM_181581.3	P1	O95620-1

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2077

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0468

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00595

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00302

AC:

477

AN:

158134

Hom.:

AF XY:

0.00257

AC XY:

223

AN XY:

86614

show subpopulations

Gnomad AFR exome

AF:

0.0509

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.000834

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000852

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000161

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.00148

AC:

2083

AN:

1409012

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

885

AN XY:

696618

show subpopulations

Gnomad4 AFR exome

AF:

0.0482

Gnomad4 AMR exome

AF:

0.00305

Gnomad4 ASJ exome

AF:

0.000594

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.0137

AC:

2083

AN:

152268

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

953

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0468

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00437

Hom.:

Bravo

AF:

0.0161

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

COG5-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 23, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

COG5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.1

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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