chr11-5755696-A-G

Position:

• chr11-5755696-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001005175.5(OR52N4):​c.956A>G​(p.Tyr319Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,612,598 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (36 hom.)
• Consequence: OR52N4 NM_001005175.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.02

Genes affected

OR52N4 (HGNC:15230): (olfactory receptor family 52 subfamily N member 4) 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]

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057881773).
• BP6: Variant 11-5755696-A-G is Benign according to our data. Variant chr11-5755696-A-G is described in ClinVar as [Benign]. Clinvar id is 731526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52N4	NM_001005175.5	c.956A>G	p.Tyr319Cys	missense_variant	2/2	ENST00000641350.2
OR52N4	XM_017017711.3	c.956A>G	p.Tyr319Cys	missense_variant	5/5
OR52N4	XM_017017713.3	c.956A>G	p.Tyr319Cys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52N4	ENST00000641350.2	c.956A>G	p.Tyr319Cys	missense_variant	2/2		NM_001005175.5	P1
TRIM5	ENST00000412903.1	c.-61-75458T>C		intron_variant		1
TRIM5	ENST00000380027.5	c.-440-70302T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152218 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00553

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00453 AC: 1118 AN: 247054 Hom.: 10 AF XY: 0.00462 AC XY: 619 AN XY: 133970

Gnomad AFR exome AF: 0.000780

Gnomad AMR exome AF: 0.000815

Gnomad ASJ exome AF: 0.000707

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00270

Gnomad FIN exome AF: 0.0178

Gnomad NFE exome AF: 0.00531

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.00477 AC: 6965 AN: 1460262 Hom.: 36 Cov.: 36 AF XY: 0.00478 AC XY: 3469 AN XY: 726322

Gnomad4 AFR exome AF: 0.000688

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.000807

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00300

Gnomad4 FIN exome AF: 0.0176

Gnomad4 NFE exome AF: 0.00488

Gnomad4 OTH exome AF: 0.00398

GnomAD4 genome AF: 0.00436 AC: 664 AN: 152336 Hom.: 6 Cov.: 33 AF XY: 0.00513 AC XY: 382 AN XY: 74486

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.00553

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00474 Hom.: 3

Bravo AF: 0.00272

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.000531 AC: 2

ESP6500EA AF: 0.00511 AC: 42

ExAC AF: 0.00470 AC: 568

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00464

EpiControl AF: 0.00463

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0023	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.41	N
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	0.97	N;N
PrimateAI	Benign	0.32	T
Polyphen		0.66	P;P
Vest4		0.19
MVP		0.41
MPC		0.044
ClinPred		0.047	T
GERP RS		3.8
Varity_R		0.086
gMVP		0.073

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs190757899; hg19: chr11-5776926; COSMIC: COSV99061095;