chr3-37296147-C-T

Position:

• chr3-37296147-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA4	NM_002078.5	c.742C>T	p.Leu248Phe	missense_variant	7/24	ENST00000361924.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA4	ENST00000361924.7	c.742C>T	p.Leu248Phe	missense_variant	7/24	1	NM_002078.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.808C>T (p.L270F) alteration is located in exon 8 (coding exon 8) of the GOLGA4 gene. This alteration results from a C to T substitution at nucleotide position 808, causing the leucine (L) at amino acid position 270 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.58	T;T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.046	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.72	N;N;.;N;N
REVEL	Benign	0.036
Sift	Benign	0.13	T;T;.;T;T
Sift4G	Benign	0.72	T;T;T;T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-37337638;