7-107564045-C-G

Variant names:

• chr7-107564045-C-G
• rs541648926
• NM_181581.3:c.-275C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_181581.3(DUS4L):​c.-275C>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 0.000318 in 1,489,040 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: DUS4L NM_181581.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.19
• Publications: 0 publications found

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: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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS4L	NM_181581.3	MANE Select	c.-275C>G		5_prime_UTR	Exon 1 of 8	NP_853559.1	O95620-1
	DUS4L-BCAP29	NM_001371364.2		c.-275C>G		5_prime_UTR	Exon 1 of 15	NP_001358293.1	A0A669KAY5
	DUS4L-BCAP29	NM_001371365.2		c.-313C>G		5_prime_UTR	Exon 1 of 14	NP_001358294.1	A0A669KB27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS4L	ENST00000265720.8	TSL:2 MANE Select	c.-275C>G		5_prime_UTR	Exon 1 of 8	ENSP00000265720.3	O95620-1
	COG5	ENST00000393603.7	TSL:1	c.-149G>C		5_prime_UTR	Exon 1 of 21	ENSP00000377228.3	A0AAA9X2X8
	DUS4L-BCAP29	ENST00000673665.1		c.-653C>G		5_prime_UTR	Exon 1 of 13	ENSP00000501082.1	A0A669KB27

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 248 AN: 148068 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000801

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: 0.00

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.000168 AC: 225 AN: 1340836 Hom.: 1 Cov.: 27 AF XY: 0.000154 AC XY: 102 AN XY: 662320

African (AFR) AF: 0.00581 AC: 176 AN: 30308

American (AMR) AF: 0.000461 AC: 16 AN: 34740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23838

East Asian (EAS) AF: 0.00 AC: 0 AN: 32446

South Asian (SAS) AF: 0.00 AC: 0 AN: 77900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36364

Middle Eastern (MID) AF: 0.000774 AC: 3 AN: 3876

European-Non Finnish (NFE) AF: 0.00000287 AC: 3 AN: 1046310

Other (OTH) AF: 0.000490 AC: 27 AN: 55054

GnomAD4 genome AF: 0.00168 AC: 249 AN: 148204 Hom.: 1 Cov.: 32 AF XY: 0.00153 AC XY: 111 AN XY: 72362

African (AFR) AF: 0.00573 AC: 234 AN: 40856

American (AMR) AF: 0.000800 AC: 12 AN: 15006

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4670

South Asian (SAS) AF: 0.00 AC: 0 AN: 4394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66752

Other (OTH) AF: 0.00145 AC: 3 AN: 2072

Alfa AF: 0.0000696 Hom.: 0

Bravo AF: 0.00201

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	COG5-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		-1.2
PromoterAI		0.056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs541648926; hg19: chr7-107204490;