rs778346804

Variant names:

• chr7-107564134-G-A
• rs778346804
• ENST00000393603.7:c.-238C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-107564134-G-A
• chr7-107564134-G-C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The ENST00000393603.7(COG5):​c.-238C>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 0.000206 in 875,762 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: COG5 ENST00000393603.7 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.213
• Publications: 0 publications found

Genes affected

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: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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000203 (147/723544) while in subpopulation MID AF = 0.00348 (9/2584). AF 95% confidence interval is 0.00182. There are 1 homozygotes in GnomAdExome4. There are 77 alleles in the male GnomAdExome4 subpopulation. Median coverage is 9. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393603.7. 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.-186G>A		5_prime_UTR	Exon 1 of 8	NP_853559.1	O95620-1
	DUS4L-BCAP29	NM_001371364.2		c.-186G>A		5_prime_UTR	Exon 1 of 15	NP_001358293.1	A0A669KAY5
	DUS4L-BCAP29	NM_001371365.2		c.-224G>A		5_prime_UTR	Exon 1 of 14	NP_001358294.1	A0A669KB27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000393603.7	TSL:1	c.-238C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000377228.3	A0AAA9X2X8
	DUS4L	ENST00000265720.8	TSL:2 MANE Select	c.-186G>A		5_prime_UTR	Exon 1 of 8	ENSP00000265720.3	O95620-1
	COG5	ENST00000393603.7	TSL:1	c.-238C>T		5_prime_UTR	Exon 1 of 21	ENSP00000377228.3	A0AAA9X2X8

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 147 AN: 723544 Hom.: 1 Cov.: 9 AF XY: 0.000208 AC XY: 77 AN XY: 370640

African (AFR) AF: 0.0000551 AC: 1 AN: 18154

American (AMR) AF: 0.00 AC: 0 AN: 24968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16696

East Asian (EAS) AF: 0.00 AC: 0 AN: 32378

South Asian (SAS) AF: 0.000531 AC: 30 AN: 56514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30530

Middle Eastern (MID) AF: 0.00348 AC: 9 AN: 2584

European-Non Finnish (NFE) AF: 0.000192 AC: 97 AN: 506516

Other (OTH) AF: 0.000284 AC: 10 AN: 35204

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74372

African (AFR) AF: 0.0000724 AC: 3 AN: 41464

American (AMR) AF: 0.000262 AC: 4 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000530 Hom.: 0

Bravo AF: 0.000230

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	COG5-congenital disorder of glycosylation (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		-0.21
PromoterAI		-0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=297/3	polymorphism

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: rs778346804; hg19: chr7-107204579;