NM_015530.5:c.749C>T

Variant names:

• chr2-170956485-C-T
• rs773448196
• NM_015530.5:c.749C>T

Variant summary

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

The NM_015530.5(GORASP2):​c.749C>T​(p.Thr250Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000484 in 1,613,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: GORASP2 NM_015530.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99
• Publications: 0 publications found

Genes affected

GORASP2 (HGNC:17500): (golgi reassembly stacking protein 2) This gene encodes a member of the Golgi reassembly stacking protein family. These proteins may play a role in the stacking of Golgi cisternae and Golgi ribbon formation, as well as Golgi fragmentation during apoptosis or mitosis. The encoded protein also plays a role in the intracellular transport of transforming growth factor alpha and may function as a molecular chaperone. A pseudogene of this gene is located on the short arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.21483898).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015530.5. 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
	GORASP2	NM_015530.5	MANE Select	c.749C>T	p.Thr250Ile	missense	Exon 7 of 10	NP_056345.3
	GORASP2	NM_001201428.2		c.545C>T	p.Thr182Ile	missense	Exon 7 of 10	NP_001188357.1	Q9H8Y8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GORASP2	ENST00000234160.5	TSL:1 MANE Select	c.749C>T	p.Thr250Ile	missense	Exon 7 of 10	ENSP00000234160.4	Q9H8Y8-1
	GORASP2	ENST00000871667.1		c.749C>T	p.Thr250Ile	missense	Exon 7 of 10	ENSP00000541726.1
	GORASP2	ENST00000972174.1		c.746C>T	p.Thr249Ile	missense	Exon 7 of 10	ENSP00000642233.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251328 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1461018 Hom.: 0 Cov.: 29 AF XY: 0.0000426 AC XY: 31 AN XY: 726926

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111332

Other (OTH) AF: 0.0000994 AC: 6 AN: 60358

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74290

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000387 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.0
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.12	T
Polyphen		0.70	P
Vest4		0.18
MutPred		0.47		Loss of glycosylation at T250 (P = 0.0335)
MVP		0.28
MPC		0.15
ClinPred		0.21	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.12
gMVP		0.44
Mutation Taster		=62/38	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: rs773448196; hg19: chr2-171812995;