3-121677424-T-C

Position:

• chr3-121677424-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366282.2(GOLGB1):​c.8900A>G​(p.His2967Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLGB1 NM_001366282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87

Genes affected

GOLGB1 (HGNC:4429): (golgin B1) Enables RNA binding activity. Involved in protein localization to pericentriolar material. Located in Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

GOLGB1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1435056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGB1	NM_001366282.2	c.8900A>G	p.His2967Arg	missense_variant	16/22	ENST00000614479.5	NP_001353211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGB1	ENST00000614479.5	c.8900A>G	p.His2967Arg	missense_variant	16/22	1	NM_001366282.2	ENSP00000484083.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000866 AC: 3 AN: 3478

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

Dec 03, 2024

The c.8885A>G (p.H2962R) alteration is located in exon 16 (coding exon 15) of the GOLGB1 gene. This alteration results from a A to G substitution at nucleotide position 8885, causing the histidine (H) at amino acid position 2962 to be replaced by an arginine (R). 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	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.019	T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.91	N;N;.
REVEL	Benign	0.034
Sift	Uncertain	0.023	D;D;.
Sift4G	Uncertain	0.050	T;T;D
Polyphen		0.10	B;.;.
Vest4		0.21
MutPred		0.12		Gain of MoRF binding (P = 0.036);.;.;
MVP		0.30
MPC		0.19
ClinPred		0.38	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-121396271;