chr7-107563979-A-C

Position:

• chr7-107563979-A-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_181581.3(DUS4L):​c.-341A>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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DUS4L NM_181581.3 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.232

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045625895).
• BP6: Variant 7-107563979-A-C is Benign according to our data. Variant chr7-107563979-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1206117.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-107563979-A-C is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUS4L	NM_181581.3	c.-341A>C		5_prime_UTR_variant	1/8	ENST00000265720.8
DUS4L-BCAP29	NR_163940.2	n.9A>C		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUS4L	ENST00000265720.8	c.-341A>C		5_prime_UTR_variant	1/8	2	NM_181581.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 43 AN: 140454 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000209

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000239

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00153

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000234

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00114 AC: 521 AN: 457192 Hom.: 0 Cov.: 24 AF XY: 0.000981 AC XY: 242 AN XY: 246802

Gnomad4 AFR exome AF: 0.000670

Gnomad4 AMR exome AF: 0.0000635

Gnomad4 ASJ exome AF: 0.000403

Gnomad4 EAS exome AF: 0.000436

Gnomad4 SAS exome AF: 0.000218

Gnomad4 FIN exome AF: 0.0000693

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.000912

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000299 AC: 42 AN: 140546 Hom.: 0 Cov.: 32 AF XY: 0.000337 AC XY: 23 AN XY: 68224

Gnomad4 AFR AF: 0.000154

Gnomad4 AMR AF: 0.000209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000239

Gnomad4 SAS AF: 0.00101

Gnomad4 FIN AF: 0.00153

Gnomad4 NFE AF: 0.000234

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.1
DANN	Benign	0.80
DEOGEN2	Benign	0.0026	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.24	T;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.17
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);
MVP		0.11
MPC		0.067
ClinPred		0.11	T
GERP RS		-1.6
Varity_R		0.052
gMVP		0.26

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: rs1203229795; hg19: chr7-107204424;