5-32126304-G-C

Variant names:

• chr5-32126304-G-C
• rs367920345
• NM_022130.4:c.805C>G

Variant summary

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

The NM_022130.4(GOLPH3):​c.805C>G​(p.Arg269Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R269W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLPH3 NM_022130.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40
• Publications: 2 publications found

Genes affected

GOLPH3 (HGNC:15452): (golgi phosphoprotein 3) 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 peripheral membrane protein of the Golgi stack and may have a regulatory role in Golgi trafficking. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3	NM_022130.4	c.805C>G	p.Arg269Gly	missense_variant	Exon 4 of 4	ENST00000265070.7	NP_071413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLPH3	ENST00000265070.7	c.805C>G	p.Arg269Gly	missense_variant	Exon 4 of 4	1	NM_022130.4	ENSP00000265070.6
GOLPH3	ENST00000503610.5	n.*587C>G		downstream_gene_variant		3		ENSP00000426752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	-0.059	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.60
Sift	Benign	0.13	T
Sift4G	Benign	0.13	T
Polyphen		0.84	P
Vest4		0.46
MVP		0.65
MPC		1.4
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.74
Mutation Taster		=37/63	disease causing

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: rs367920345; hg19: chr5-32126410;