3-39098746-C-A

Variant names:

• chr3-39098746-C-A
• rs139163342
• NM_031899.4:c.1064G>T

Variant summary

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

The NM_031899.4(GORASP1):​c.1064G>T​(p.Arg355Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GORASP1 NM_031899.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 1 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: 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=0.28112563).

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.1064G>T	p.Arg355Leu	missense	Exon 8 of 9	NP_114105.1	Q9BQQ3-1
	GORASP1	NM_001410726.1		c.974G>T	p.Arg325Leu	missense	Exon 8 of 9	NP_001397655.1	A0A8Q3SHU6
	GORASP1	NM_001410731.1		c.884G>T	p.Arg295Leu	missense	Exon 7 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.1064G>T	p.Arg355Leu	missense	Exon 8 of 9	ENSP00000313869.3	Q9BQQ3-1
	GORASP1	ENST00000452389.7	TSL:1	n.*375G>T		non_coding_transcript_exon	Exon 8 of 9	ENSP00000403167.2	Q9BQQ3-2
	GORASP1	ENST00000453680.6	TSL:1	n.*64G>T		non_coding_transcript_exon	Exon 8 of 9	ENSP00000392020.1	G3V0G1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.076
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.54	T
Polyphen		0.69	P
Vest4		0.62
MutPred		0.43		Loss of methylation at R355 (P = 0.0142)
MVP		0.23
MPC		0.42
ClinPred		0.78	D
GERP RS		2.8
Varity_R		0.14
gMVP		0.23
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs139163342; hg19: chr3-39140237;