rs41302045

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-117578909-C-T
• chr6-117578909-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_020399.4(GOPC):​c.441G>A​(p.Lys147Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,587,216 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (25 hom.)
• Consequence: GOPC NM_020399.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500
• Publications: 2 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 6-117578909-C-T is Benign according to our data. Variant chr6-117578909-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2656876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.05 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00421 (6047/1435044) while in subpopulation MID AF = 0.0239 (135/5656). AF 95% confidence interval is 0.0206. There are 25 homozygotes in GnomAdExome4. There are 3011 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 25 Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOPC	NM_020399.4	MANE Select	c.441G>A	p.Lys147Lys	synonymous	Exon 2 of 9	NP_065132.1	Q9HD26-1
	GOPC	NM_001017408.3		c.441G>A	p.Lys147Lys	synonymous	Exon 2 of 8	NP_001017408.1	Q9HD26-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOPC	ENST00000368498.7	TSL:1 MANE Select	c.441G>A	p.Lys147Lys	synonymous	Exon 2 of 9	ENSP00000357484.2	Q9HD26-1
	GOPC	ENST00000052569.10	TSL:1	c.441G>A	p.Lys147Lys	synonymous	Exon 2 of 8	ENSP00000052569.6	Q9HD26-2
	GOPC	ENST00000535237.2	TSL:1	c.441G>A	p.Lys147Lys	synonymous	Exon 2 of 8	ENSP00000445690.2	F5H1Y4

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00243

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00436

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00370 AC: 861 AN: 232896 AF XY: 0.00403

Gnomad AFR exome AF: 0.000456

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000332

Gnomad NFE exome AF: 0.00494

Gnomad OTH exome AF: 0.00676

GnomAD4 exome AF: 0.00421 AC: 6047 AN: 1435044 Hom.: 25 Cov.: 30 AF XY: 0.00422 AC XY: 3011 AN XY: 712772

African (AFR) AF: 0.00114 AC: 37 AN: 32496

American (AMR) AF: 0.00289 AC: 117 AN: 40454

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 321 AN: 25360

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

South Asian (SAS) AF: 0.00334 AC: 272 AN: 81500

European-Finnish (FIN) AF: 0.000511 AC: 27 AN: 52842

Middle Eastern (MID) AF: 0.0239 AC: 135 AN: 5656

European-Non Finnish (NFE) AF: 0.00441 AC: 4848 AN: 1099062

Other (OTH) AF: 0.00490 AC: 290 AN: 59180

GnomAD4 genome AF: 0.00292 AC: 444 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.00289 AC XY: 215 AN XY: 74396

African (AFR) AF: 0.000626 AC: 26 AN: 41540

American (AMR) AF: 0.00242 AC: 37 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4830

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00436 AC: 296 AN: 67954

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00443 Hom.: 2

Bravo AF: 0.00311

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	10
DANN	Benign	0.64
PhyloP100		-0.050
Mutation Taster		=100/0	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; COSMIC: COSV50004690;