NM_002078.5:c.742C>T

Variant names:

• chr3-37296147-C-T
• NM_002078.5:c.742C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002078.5(GOLGA4):​c.742C>T​(p.Leu248Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLGA4 NM_002078.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.384
• Publications: 0 publications found

Genes affected

GOLGA4 (HGNC:4427): (golgin A4) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This protein has been postulated to play a role in Rab6-regulated membrane-tethering events in the Golgi apparatus. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045980304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002078.5. 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
	GOLGA4	NM_002078.5	MANE Select	c.742C>T	p.Leu248Phe	missense	Exon 7 of 24	NP_002069.2
	GOLGA4	NM_001429190.1		c.859C>T	p.Leu287Phe	missense	Exon 8 of 24	NP_001416119.1
	GOLGA4	NM_001429191.1		c.808C>T	p.Leu270Phe	missense	Exon 8 of 25	NP_001416120.1	A0A8V8TQI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA4	ENST00000361924.7	TSL:1 MANE Select	c.742C>T	p.Leu248Phe	missense	Exon 7 of 24	ENSP00000354486.2	Q13439-1
	GOLGA4	ENST00000437131.2	TSL:1	c.808C>T	p.Leu270Phe	missense	Exon 8 of 24	ENSP00000405842.2	H0Y6I0
	GOLGA4	ENST00000356847.8	TSL:1	c.808C>T	p.Leu270Phe	missense	Exon 8 of 23	ENSP00000349305.4	Q13439-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.064
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.42
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		0.38
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.036
Sift	Benign	0.13	T
Sift4G	Benign	0.72	T
Polyphen		0.0010	B
Vest4		0.051
MutPred		0.15		Loss of ubiquitination at K246 (P = 0.0954)
MVP		0.18
MPC		0.048
ClinPred		0.030	T
GERP RS		1.6
Varity_R		0.022
gMVP		0.051
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

hg19: chr3-37337638;