Genetic Variant NM_014373.3:c.64C>A (chr3-170084036-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_014373.3(GPR160):c.64C>A(p.Leu22Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000832 in 1,578,902 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00062 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 19 hom. )

Consequence

GPR160
NM_014373.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0410

Publications

0 publications found

Variant links:

Genes affected

GPR160 (HGNC:23693): (G protein-coupled receptor 160) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

GPR160 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040305555).

BP6

Variant 3-170084036-C-A is Benign according to our data. Variant chr3-170084036-C-A is described in ClinVar as Benign. ClinVar VariationId is 3038858.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000624 (95/152274) while in subpopulation SAS AF = 0.0191 (92/4828). AF 95% confidence interval is 0.0159. There are 2 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014373.3. 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
	GPR160	NM_014373.3	MANE Select	c.64C>A	p.Leu22Ile	missense	Exon 4 of 4	NP_055188.1	Q9UJ42

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR160	ENST00000355897.10	TSL:1 MANE Select	c.64C>A	p.Leu22Ile	missense	Exon 4 of 4	ENSP00000348161.5	Q9UJ42
GPR160	ENST00000492492.5	TSL:1	c.64C>A	p.Leu22Ile	missense	Exon 5 of 5	ENSP00000418531.1	C9J0J1
GPR160	ENST00000900470.1		c.64C>A	p.Leu22Ile	missense	Exon 4 of 4	ENSP00000570529.1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00171

AC:

384

AN:

225036

AF XY:

0.00243

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000950

Gnomad OTH exome

AF:

0.000187

GnomAD4 exome

AF:

0.000854

AC:

1218

AN:

1426628

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

882

AN XY:

709148

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31694

American (AMR)

AF:

0.00

AC:

AN:

37794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24508

East Asian (EAS)

AF:

0.00

AC:

AN:

39300

South Asian (SAS)

AF:

0.0145

AC:

1161

AN:

79886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52524

Middle Eastern (MID)

AF:

0.000714

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.00000365

AC:

AN:

1096458

Other (OTH)

AF:

0.000815

AC:

AN:

58862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000624

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41538

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0191

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000517

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00196

AC:

238

Asia WGS

AF:

0.00549

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GPR160-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.096

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

0.041

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

REVEL

Benign

0.018

Sift

Benign

0.12

Sift4G

Benign

0.34

Polyphen

0.70

Vest4

0.33

MutPred

0.28

Gain of catalytic residue at L27 (P = 0.0705)

MVP

0.014

MPC

0.23

ClinPred

0.024

GERP RS

2.5

Varity_R

0.082

gMVP

0.054

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over