chr6-117578909-C-G

Variant names:

• chr6-117578909-C-G
• rs41302045
• NM_020399.4:c.441G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 0 publications found

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)

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020399.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOPC	NM_020399.4	MANE Select	c.441G>C	p.Lys147Asn	missense	Exon 2 of 9	NP_065132.1
	GOPC	NM_001017408.3		c.441G>C	p.Lys147Asn	missense	Exon 2 of 8	NP_001017408.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOPC	ENST00000368498.7	TSL:1 MANE Select	c.441G>C	p.Lys147Asn	missense	Exon 2 of 9	ENSP00000357484.2
	GOPC	ENST00000052569.10	TSL:1	c.441G>C	p.Lys147Asn	missense	Exon 2 of 8	ENSP00000052569.6
	GOPC	ENST00000535237.2	TSL:1	c.441G>C	p.Lys147Asn	missense	Exon 2 of 8	ENSP00000445690.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435078 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712788

African (AFR) AF: 0.00 AC: 0 AN: 32496

American (AMR) AF: 0.00 AC: 0 AN: 40454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25360

East Asian (EAS) AF: 0.00 AC: 0 AN: 38494

South Asian (SAS) AF: 0.00 AC: 0 AN: 81506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52844

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5658

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099086

Other (OTH) AF: 0.00 AC: 0 AN: 59180

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.050
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.20		Loss of ubiquitination at K147 (P = 0.0087)
MVP		0.92
MPC		0.72
ClinPred		0.95	D
GERP RS		2.1
Varity_R		0.46
gMVP		0.49
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs41302045; hg19: chr6-117900072;