6-117675486-G-A

Position:

• chr6-117675486-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000368494.4(NUS1):​c.-185G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00268 in 614,824 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (14 hom., cov: 31)
  • Exomes 𝑓: 0.00090 (5 hom.)
• Consequence: NUS1 ENST00000368494.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.06

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 6-117675486-G-A is Benign according to our data. Variant chr6-117675486-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1706275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00818 (1230/150356) while in subpopulation AFR AF= 0.028 (1158/41392). AF 95% confidence interval is 0.0266. There are 14 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUS1	NM_138459.5	c.-185G>A		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.-185G>A		5_prime_UTR_variant	1/5	1	NM_138459.5	ENSP00000357480	P1

Frequencies

GnomAD3 genomes AF: 0.00812 AC: 1220 AN: 150236 Hom.: 14 Cov.: 31

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00336

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000752

Gnomad OTH AF: 0.00673

GnomAD4 exome AF: 0.000902 AC: 419 AN: 464468 Hom.: 5 Cov.: 5 AF XY: 0.000721 AC XY: 178 AN XY: 246934

Gnomad4 AFR exome AF: 0.0269

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000658

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000739

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00818 AC: 1230 AN: 150356 Hom.: 14 Cov.: 31 AF XY: 0.00792 AC XY: 583 AN XY: 73610

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.00336

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000752

Gnomad4 OTH AF: 0.00666

Alfa AF: 0.00596 Hom.: 0

Bravo AF: 0.00923

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs192920839; hg19: chr6-117996649;