chr3-37281968-C-T

Position:

• chr3-37281968-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002078.5(GOLGA4):​c.173C>T​(p.Thr58Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,611,550 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (53 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (48 hom.)
• Consequence: GOLGA4 NM_002078.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.366

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]

GOLGA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015317202).
• BP6: Variant 3-37281968-C-T is Benign according to our data. Variant chr3-37281968-C-T is described in ClinVar as [Benign]. Clinvar id is 710917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA4	NM_002078.5	c.173C>T	p.Thr58Ile	missense_variant	3/24	ENST00000361924.7	NP_002069.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA4	ENST00000361924.7	c.173C>T	p.Thr58Ile	missense_variant	3/24	1	NM_002078.5	ENSP00000354486.2

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2284 AN: 152168 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00412 AC: 1027 AN: 249032 Hom.: 26 AF XY: 0.00308 AC XY: 416 AN XY: 135008

Gnomad AFR exome AF: 0.0564

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000657

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000329

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00165 AC: 2412 AN: 1459264 Hom.: 48 Cov.: 31 AF XY: 0.00149 AC XY: 1079 AN XY: 725672

Gnomad4 AFR exome AF: 0.0536

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.0150 AC: 2284 AN: 152286 Hom.: 53 Cov.: 32 AF XY: 0.0142 AC XY: 1054 AN XY: 74472

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00262 Hom.: 10

Bravo AF: 0.0175

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0502 AC: 221

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00488 AC: 593

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T;.;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.76	T;T;T;T;T
MetaRNN	Benign	0.0015	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N;D;N;N;D
REVEL	Benign	0.046
Sift	Benign	0.082	T;D;T;T;D
Sift4G	Benign	0.061	T;T;T;T;D
Polyphen		0.54	P;B;.;P;.
Vest4		0.39
MVP		0.27
MPC		0.053
ClinPred		0.013	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60600531; hg19: chr3-37323459;