chr3-39099365-C-T

Variant names:

• chr3-39099365-C-T
• rs145676119
• NM_031899.4:c.904G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_031899.4(GORASP1):​c.904G>A​(p.Val302Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000579 in 1,613,170 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (4 hom.)
• Consequence: GORASP1 NM_031899.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.24
• Publications: 4 publications found

Genes affected

GORASP1 (HGNC:16769): (golgi reassembly stacking protein 1) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a membrane protein involved in establishing the stacked structure of the Golgi apparatus. It is a caspase-3 substrate, and cleavage of this encoded protein contributes to Golgi fragmentation in apoptosis. This encoded protein can form a complex with the Golgi matrix protein GOLGA2, and this complex binds to the vesicle docking protein p115. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11925006).
• BS2: High Homozygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031899.4. 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
	GORASP1	NM_031899.4	MANE Select	c.904G>A	p.Val302Ile	missense	Exon 7 of 9	NP_114105.1	Q9BQQ3-1
	GORASP1	NM_001410726.1		c.814G>A	p.Val272Ile	missense	Exon 7 of 9	NP_001397655.1	A0A8Q3SHU6
	GORASP1	NM_001410731.1		c.724G>A	p.Val242Ile	missense	Exon 6 of 8	NP_001397660.1	A0A8Q3WL08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GORASP1	ENST00000319283.8	TSL:1 MANE Select	c.904G>A	p.Val302Ile	missense	Exon 7 of 9	ENSP00000313869.3	Q9BQQ3-1
	GORASP1	ENST00000452389.7	TSL:1	n.*215G>A		non_coding_transcript_exon	Exon 7 of 9	ENSP00000403167.2	Q9BQQ3-2
	GORASP1	ENST00000453680.6	TSL:1	n.855G>A		non_coding_transcript_exon	Exon 7 of 9	ENSP00000392020.1	G3V0G1

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000289 AC: 72 AN: 249512 AF XY: 0.000311

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.0000875

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000586

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000593 AC: 866 AN: 1460840 Hom.: 4 Cov.: 31 AF XY: 0.000568 AC XY: 413 AN XY: 726712

African (AFR) AF: 0.0000599 AC: 2 AN: 33396

American (AMR) AF: 0.0000899 AC: 4 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.000745 AC: 828 AN: 1111572

Other (OTH) AF: 0.000381 AC: 23 AN: 60312

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74482

African (AFR) AF: 0.000168 AC: 7 AN: 41576

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000867 AC: 59 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000516 Hom.: 0

Bravo AF: 0.000389

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000338 AC: 41

EpiCase AF: 0.000327

EpiControl AF: 0.000534

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	-0.033	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.38
MVP		0.69
MPC		0.51
ClinPred		0.12	T
GERP RS		5.2
Varity_R		0.18
gMVP		0.18
Mutation Taster		=71/29	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: rs145676119; hg19: chr3-39140856;