3-37282133-G-T

Variant names:

• chr3-37282133-G-T
• rs748127866
• NM_002078.5:c.338G>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.338G>T​(p.Ser113Ile) 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. 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. S113N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLGA4 NM_002078.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• 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=0.036551625).

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.338G>T	p.Ser113Ile	missense	Exon 3 of 24	NP_002069.2
	GOLGA4	NM_001429190.1		c.503G>T	p.Ser168Ile	missense	Exon 5 of 24	NP_001416119.1
	GOLGA4	NM_001429191.1		c.404G>T	p.Ser135Ile	missense	Exon 4 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.338G>T	p.Ser113Ile	missense	Exon 3 of 24	ENSP00000354486.2	Q13439-1
	GOLGA4	ENST00000437131.2	TSL:1	c.404G>T	p.Ser135Ile	missense	Exon 4 of 24	ENSP00000405842.2	H0Y6I0
	GOLGA4	ENST00000356847.8	TSL:1	c.404G>T	p.Ser135Ile	missense	Exon 4 of 23	ENSP00000349305.4	Q13439-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.0
DANN	Benign	0.91
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.89
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Uncertain	0.049	D
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.12		Loss of phosphorylation at S113 (P = 0.0059)
MVP		0.18
MPC		0.054
ClinPred		0.087	T
GERP RS		2.8
PromoterAI		0.12	Neutral
Varity_R		0.099
gMVP		0.16
Mutation Taster		=86/14	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: rs748127866; hg19: chr3-37323624;