3-168010367-G-A

Variant names:

• chr3-168010367-G-A
• rs200359669
• NM_014498.5:c.1993C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014498.5(GOLIM4):​c.1993C>T​(p.Arg665Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,612,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R665L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (1 hom.)
• Consequence: GOLIM4 NM_014498.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

Genes affected

GOLIM4 (HGNC:15448): (golgi integral membrane protein 4) 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 type II Golgi-resident protein. It may process proteins synthesized in the rough endoplasmic reticulum and assist in the transport of protein cargo through the Golgi apparatus. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14363715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014498.5. 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
	GOLIM4	NM_014498.5	MANE Select	c.1993C>T	p.Arg665Cys	missense	Exon 16 of 16	NP_055313.1	O00461
	GOLIM4	NM_001308155.2		c.1909C>T	p.Arg637Cys	missense	Exon 15 of 15	NP_001295084.1	F8W785

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLIM4	ENST00000470487.6	TSL:1 MANE Select	c.1993C>T	p.Arg665Cys	missense	Exon 16 of 16	ENSP00000417354.1	O00461
	GOLIM4	ENST00000309027.4	TSL:1	c.1909C>T	p.Arg637Cys	missense	Exon 15 of 15	ENSP00000309893.4	F8W785
	GOLIM4	ENST00000852499.1		c.2029C>T	p.Arg677Cys	missense	Exon 16 of 16	ENSP00000522558.1

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251000 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000793

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000541 AC: 79 AN: 1460106 Hom.: 1 Cov.: 29 AF XY: 0.0000509 AC XY: 37 AN XY: 726434

African (AFR) AF: 0.000120 AC: 4 AN: 33446

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000630 AC: 70 AN: 1110570

Other (OTH) AF: 0.0000332 AC: 2 AN: 60322

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74236

African (AFR) AF: 0.000121 AC: 5 AN: 41438

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

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.096
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.019
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.13
MVP		0.58
MPC		0.39
ClinPred		0.14	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.012
Mutation Taster		=94/6	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: rs200359669; hg19: chr3-167728155;