chr6-117675655-T-C

Position:

• chr6-117675655-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138459.5(NUS1):​c.-16T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 148,260 control chromosomes in the GnomAD database, including 67,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (67057 hom., cov: 22)
  • Exomes 𝑓: 0.99 (587666 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUS1 NM_138459.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.860

Genes affected

NUS1 (HGNC:21042): (NUS1 dehydrodolichyl diphosphate synthase subunit) This gene encodes a type I single transmembrane domain receptor, which is a subunit of cis-prenyltransferase, and serves as a specific receptor for the neural and cardiovascular regulator Nogo-B. The encoded protein is essential for dolichol synthesis and protein glycosylation. This gene is highly expressed in non-small cell lung carcinomas as well as estrogen receptor-alpha positive breast cancer cells where it promotes epithelial mesenchymal transition. This gene is associated with the poor prognosis of human hepatocellular carcinoma patients. Naturally occurring mutations in this gene cause a congenital disorder of glycosylation and are associated with epilepsy. A knockout of the orthologous gene in mice causes embryonic lethality before day 6.5. Pseudogenes of this gene have been defined on chromosomes 13 and X. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-117675655-T-C is Benign according to our data. Variant chr6-117675655-T-C is described in ClinVar as [Benign]. Clinvar id is 1327053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUS1	NM_138459.5	c.-16T>C		5_prime_UTR_variant	1/5	ENST00000368494.4	NP_612468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUS1	ENST00000368494.4	c.-16T>C		5_prime_UTR_variant	1/5	1	NM_138459.5	ENSP00000357480	P1

Frequencies

GnomAD3 genomes AF: 0.949 AC: 140599 AN: 148162 Hom.: 67016 Cov.: 22

Gnomad AFR AF: 0.857

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.990

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.956

GnomAD3 exomes AF: 0.948 AC: 112478 AN: 118648 Hom.: 54098 AF XY: 0.957 AC XY: 61976 AN XY: 64764

Gnomad AFR exome AF: 0.756

Gnomad AMR exome AF: 0.914

Gnomad ASJ exome AF: 0.997

Gnomad EAS exome AF: 0.780

Gnomad SAS exome AF: 0.993

Gnomad FIN exome AF: 0.972

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.978

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.987 AC: 1188454 AN: 1204086 Hom.: 587666 Cov.: 17 AF XY: 0.988 AC XY: 595258 AN XY: 602536

Gnomad4 AFR exome AF: 0.854

Gnomad4 AMR exome AF: 0.926

Gnomad4 ASJ exome AF: 0.998

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.994

Gnomad4 FIN exome AF: 0.981

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.978

GnomAD4 genome AF: 0.949 AC: 140689 AN: 148260 Hom.: 67057 Cov.: 22 AF XY: 0.948 AC XY: 68457 AN XY: 72192

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.957

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.954

Alfa AF: 0.975 Hom.: 13074

Bravo AF: 0.941

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 55, with seizures Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Congenital disorder of glycosylation, type IAA Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9767451; hg19: chr6-117996818; COSMIC: COSV63844470;