chr3-37273555-C-T

Variant names:

• chr3-37273555-C-T
• rs373401405
• ENST00000437131.2:c.182C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001429190.1(GOLGA4):​c.281C>T​(p.Ser94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,512,854 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: GOLGA4 NM_001429190.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.556
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042024553).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429190.1. 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.163-8403C>T		intron	N/A	NP_002069.2
	GOLGA4	NM_001429190.1		c.281C>T	p.Ser94Leu	missense	Exon 4 of 24	NP_001416119.1
	GOLGA4	NM_001429191.1		c.182C>T	p.Ser61Leu	missense	Exon 3 of 25	NP_001416120.1	A0A8V8TQI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA4	ENST00000437131.2	TSL:1	c.182C>T	p.Ser61Leu	missense	Exon 3 of 24	ENSP00000405842.2	H0Y6I0
	GOLGA4	ENST00000356847.8	TSL:1	c.182C>T	p.Ser61Leu	missense	Exon 3 of 23	ENSP00000349305.4	Q13439-5
	GOLGA4	ENST00000429018.5	TSL:1	c.182C>T	p.Ser61Leu	missense	Exon 3 of 5	ENSP00000403009.1	C9JHJ5

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 247 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00538

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000261 AC: 36 AN: 138190 AF XY: 0.000134

Gnomad AFR exome AF: 0.00453

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000235

GnomAD4 exome AF: 0.000124 AC: 169 AN: 1360620 Hom.: 1 Cov.: 25 AF XY: 0.000106 AC XY: 71 AN XY: 672958

African (AFR) AF: 0.00420 AC: 131 AN: 31154

American (AMR) AF: 0.000308 AC: 11 AN: 35666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25060

East Asian (EAS) AF: 0.00 AC: 0 AN: 35598

South Asian (SAS) AF: 0.0000254 AC: 2 AN: 78758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34024

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5652

European-Non Finnish (NFE) AF: 0.00000284 AC: 3 AN: 1057514

Other (OTH) AF: 0.000332 AC: 19 AN: 57194

GnomAD4 genome AF: 0.00170 AC: 259 AN: 152234 Hom.: 3 Cov.: 32 AF XY: 0.00168 AC XY: 125 AN XY: 74450

African (AFR) AF: 0.00566 AC: 235 AN: 41542

American (AMR) AF: 0.00124 AC: 19 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00280 Hom.: 0

Bravo AF: 0.00193

ExAC AF: 0.000107 AC: 2

Asia WGS AF: 0.00173 AC: 6 AN: 3478

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	0.066
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.8
DANN	Benign	0.60
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.56
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.035
Sift	Benign	0.41	T
Sift4G	Benign	0.081	T
Polyphen		0.0030	B
Vest4		0.034
MVP		0.048
MPC		0.041
ClinPred		0.0030	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.078
Mutation Taster		=96/4	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: rs373401405; hg19: chr3-37315046;