6-29555933-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_006398.4(UBD):c.445G>A(p.Gly149Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,613,056 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (6 hom.)
• Consequence: UBD NM_006398.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.898

Genes affected

UBD (HGNC:18795): (ubiquitin D) This gene encodes a protein which contains two ubiquitin-like domains and appears to have similar function to ubiquitin. Through covalent attachment, the encoded protein targets other proteins for 26S proteasome degradation. This protein has been implicated to function in many cellular processes, including caspase-dependent apoptosis, formation of aggresomes, mitotic regulation, and dendritic cell maturation. Upregulation of this gene may promote inflammation in chronic kidney disease and has been observed in many cancer types. [provided by RefSeq, Aug 2017]

OR2I1P (HGNC:8258): (olfactory receptor family 2 subfamily I member 1 pseudogene) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010159671).
• BP6: Variant 6-29555933-C-T is Benign according to our data. Variant chr6-29555933-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 749159.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBD	NM_006398.4	c.445G>A	p.Gly149Ser	missense_variant	2/2	ENST00000377050.5
OR2I1P	NM_001396058.1	c.*1767C>T		3_prime_UTR_variant	2/2	ENST00000641137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBD	ENST00000377050.5	c.445G>A	p.Gly149Ser	missense_variant	2/2	1	NM_006398.4	P1
OR2I1P	ENST00000641137.2	c.*1767C>T		3_prime_UTR_variant	2/2		NM_001396058.1	P1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000401 AC: 99 AN: 246738 Hom.: 1 AF XY: 0.000565 AC XY: 76 AN XY: 134438

Gnomad AFR exome AF: 0.000198

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00280

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000812

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000171 AC: 250 AN: 1460772 Hom.: 6 Cov.: 53 AF XY: 0.000238 AC XY: 173 AN XY: 726702

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00219

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000306

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74454

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000575 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.000490 AC: 58

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Invitae

Jun 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.3
Dann	Benign	0.56
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0046	N
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.027
Sift	Benign	0.036	D
Sift4G	Benign	0.35	T
Polyphen		0.027	B
Vest4		0.090
MVP		0.014
MPC		0.20
ClinPred		0.0067	T
GERP RS		-7.4
Varity_R		0.059
gMVP		0.14

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: rs544222490; hg19: chr6-29523710; COSMIC: COSV63544142;