7-107563996-A-T

Variant names:

• chr7-107563996-A-T
• rs536210903
• NM_181581.3:c.-324A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181581.3(DUS4L):​c.-324A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000903 in 1,107,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: DUS4L NM_181581.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.92
• 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]

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]

COG5 Gene-Disease associations (from GenCC):

• COG5-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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.-324A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_853559.1	O95620-1
	DUS4L	NM_181581.3	MANE Select	c.-324A>T		5_prime_UTR	Exon 1 of 8	NP_853559.1	O95620-1
	DUS4L-BCAP29	NM_001371364.2		c.-324A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001358293.1	A0A669KAY5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUS4L	ENST00000265720.8	TSL:2 MANE Select	c.-324A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000265720.3	O95620-1
	DUS4L-BCAP29	ENST00000673665.1		c.-702A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000501082.1	A0A669KB27
	DUS4L	ENST00000265720.8	TSL:2 MANE Select	c.-324A>T		5_prime_UTR	Exon 1 of 8	ENSP00000265720.3	O95620-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.03e-7 AC: 1 AN: 1107754 Hom.: 0 Cov.: 35 AF XY: 0.00000182 AC XY: 1 AN XY: 550120

African (AFR) AF: 0.00 AC: 0 AN: 25168

American (AMR) AF: 0.00 AC: 0 AN: 31602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17532

East Asian (EAS) AF: 0.00 AC: 0 AN: 18370

South Asian (SAS) AF: 0.00 AC: 0 AN: 75728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2920

European-Non Finnish (NFE) AF: 0.00000116 AC: 1 AN: 863732

Other (OTH) AF: 0.00 AC: 0 AN: 41874

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.036
DANN	Benign	0.49
PhyloP100		-4.9
PromoterAI		-0.13	Neutral
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

Other links and lift over

dbSNP: rs536210903; hg19: chr7-107204441;