chr7-107563975-G-C

Position:

• chr7-107563975-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_181581.3(DUS4L):​c.-345G>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 (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUS4L NM_181581.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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]

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]

DUS4L-BCAP29 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-107563975-G-C is Benign according to our data. Variant chr7-107563975-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3042839.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-107563975-G-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUS4L	NM_181581.3	c.-345G>C		5_prime_UTR_variant	1/8	ENST00000265720.8
DUS4L-BCAP29	NR_163940.2	n.5G>C		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUS4L	ENST00000265720.8	c.-345G>C		5_prime_UTR_variant	1/8	2	NM_181581.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 83 AN: 144604 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000916

Gnomad SAS AF: 0.00144

Gnomad FIN AF: 0.00195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000473

Gnomad OTH AF: 0.000495

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00424 AC: 2223 AN: 524544 Hom.: 0 Cov.: 28 AF XY: 0.00371 AC XY: 1035 AN XY: 278622

Gnomad4 AFR exome AF: 0.00271

Gnomad4 AMR exome AF: 0.000191

Gnomad4 ASJ exome AF: 0.000855

Gnomad4 EAS exome AF: 0.00130

Gnomad4 SAS exome AF: 0.000870

Gnomad4 FIN exome AF: 0.000276

Gnomad4 NFE exome AF: 0.00598

Gnomad4 OTH exome AF: 0.00385

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000567 AC: 82 AN: 144734 Hom.: 0 Cov.: 32 AF XY: 0.000681 AC XY: 48 AN XY: 70438

Gnomad4 AFR AF: 0.000447

Gnomad4 AMR AF: 0.000341

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000916

Gnomad4 SAS AF: 0.00119

Gnomad4 FIN AF: 0.00195

Gnomad4 NFE AF: 0.000473

Gnomad4 OTH AF: 0.000489

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

COG5-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 23, 2020

This variant is classified as likely 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	-0.83
CADD	Benign	11
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1462066599; hg19: chr7-107204420;