7-107563988-A-C

Position:

• chr7-107563988-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_181581.3(DUS4L):​c.-332A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUS4L NM_181581.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.268

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-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]

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUS4L	NM_181581.3	c.-332A>C		5_prime_UTR_premature_start_codon_gain_variant	1/8	ENST00000265720.8	NP_853559.1
DUS4L	NM_181581.3	c.-332A>C		5_prime_UTR_variant	1/8	ENST00000265720.8	NP_853559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUS4L	ENST00000265720	c.-332A>C		5_prime_UTR_premature_start_codon_gain_variant	1/8	2	NM_181581.3	ENSP00000265720.3
DUS4L-BCAP29	ENST00000673757	c.-332A>C		5_prime_UTR_premature_start_codon_gain_variant	1/15			ENSP00000501026.1
DUS4L	ENST00000265720	c.-332A>C		5_prime_UTR_variant	1/8	2	NM_181581.3	ENSP00000265720.3
DUS4L-BCAP29	ENST00000673757	c.-332A>C		5_prime_UTR_variant	1/15			ENSP00000501026.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 138954 Hom.: 0 Cov.: 32 FAILED QC

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000185 AC: 1 AN: 540142 Hom.: 0 Cov.: 27 AF XY: 0.00000351 AC XY: 1 AN XY: 284716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000285

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 139082 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 67390

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

COG5-congenital disorder of glycosylation Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 22, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with COG5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the COG5 mRNA. The next in-frame methionine is located at codon 32. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.5
DANN	Benign	0.75
DEOGEN2	Benign	0.0030	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.00093	T
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.24	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.041	D;D;D
Sift4G	Benign	0.061	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.17
MutPred		0.94		Gain of methylation at M1 (P = 0.0352);Gain of methylation at M1 (P = 0.0352);Gain of methylation at M1 (P = 0.0352);
MVP		0.28
ClinPred		0.27	T
GERP RS		-7.6
Varity_R		0.40
gMVP		0.35

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

Other links and lift over

dbSNP: rs748922374; hg19: chr7-107204433;