3-121677426-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001366282.2(GOLGB1):c.8898A>G(p.Ile2966Met) 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: GOLGB1 NM_001366282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.48

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]

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=0.016091913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGB1	NM_001366282.2	c.8898A>G	p.Ile2966Met	missense_variant	16/22	ENST00000614479.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGB1	ENST00000614479.5	c.8898A>G	p.Ile2966Met	missense_variant	16/22	1	NM_001366282.2	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 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

Aug 03, 2022

The c.8883A>G (p.I2961M) 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 8883, causing the isoleucine (I) at amino acid position 2961 to be replaced by a methionine (M). 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	0.052
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.39
Dann	Benign	0.27
DEOGEN2	Benign	0.0065	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.016	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.6	N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.060	N;N;.
REVEL	Benign	0.010
Sift	Benign	0.21	T;T;.
Sift4G	Benign	0.17	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.060
MutPred		0.15		Gain of MoRF binding (P = 0.0854);.;.;
MVP		0.13
MPC		0.11
ClinPred		0.061	T
GERP RS		-6.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.10

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: chr3-121396273;