dbSNP rs41302045: GOPC:p.Lys147Asn (chr6-117578909-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020399.4(GOPC):c.441G>C(p.Lys147Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K147K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GOPC
NM_020399.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0500

Publications

0 publications found

Variant links:

Genes affected

GOPC (HGNC:17643): (golgi associated PDZ and coiled-coil motif containing) This gene encodes a Golgi protein with a PDZ domain. The PDZ domain is globular and proteins which contain them bind other proteins through short motifs near the C-termini. Mice which are deficient in the orthologous protein have globozoospermia and are infertile. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

GOPC Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

GOPC links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27703875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOPC	NM_020399.4 link	c.441G>C	p.Lys147Asn	missense_variant	Exon 2 of 9	ENST00000368498.7	NP_065132.1	Q9HD26-1
GOPC	NM_001017408.3 link	c.441G>C	p.Lys147Asn	missense_variant	Exon 2 of 8		NP_001017408.1	Q9HD26-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GOPC	ENST00000368498.7 link	c.441G>C	p.Lys147Asn	missense_variant	Exon 2 of 9	1	NM_020399.4	ENSP00000357484.2	Q9HD26-1
GOPC	ENST00000052569.10 link	c.441G>C	p.Lys147Asn	missense_variant	Exon 2 of 8	1		ENSP00000052569.6	Q9HD26-2
GOPC	ENST00000535237.2 link	c.441G>C	p.Lys147Asn	missense_variant	Exon 2 of 8	1		ENSP00000445690.2	F5H1Y4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435078

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32496

American (AMR)

AF:

0.00

AC:

AN:

40454

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25360

East Asian (EAS)

AF:

0.00

AC:

AN:

38494

South Asian (SAS)

AF:

0.00

AC:

AN:

81506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52844

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099086

Other (OTH)

AF:

0.00

AC:

AN:

59180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.051

MetaRNN

Benign

0.28

T;T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Uncertain

2.3

M;M;.

PhyloP100

-0.050

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;D;T

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.37

MutPred

0.20

Loss of ubiquitination at K147 (P = 0.0087);Loss of ubiquitination at K147 (P = 0.0087);Loss of ubiquitination at K147 (P = 0.0087);

MVP

0.92

MPC

0.72

ClinPred

0.95

GERP RS

2.1

Varity_R

0.46

gMVP

0.49

Mutation Taster

=54/46

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over