3-121677412-A-G

Variant summary

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

The NM_001366282.2(GOLGB1):c.8912T>C(p.Met2971Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GOLGB1 NM_001366282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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 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=0.17775148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGB1	NM_001366282.2	c.8912T>C	p.Met2971Thr	missense_variant	16/22	ENST00000614479.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGB1	ENST00000614479.5	c.8912T>C	p.Met2971Thr	missense_variant	16/22	1	NM_001366282.2	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251108 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135734

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456352 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Oct 05, 2021

The c.8897T>C (p.M2966T) alteration is located in exon 16 (coding exon 15) of the GOLGB1 gene. This alteration results from a T to C substitution at nucleotide position 8897, causing the methionine (M) at amino acid position 2966 to be replaced by a threonine (T). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	22
Dann	Benign	0.58
DEOGEN2	Benign	0.024	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.0019
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.9	N;N;.
REVEL	Benign	0.059
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.18	B;.;.
Vest4		0.51
MutPred		0.25		Gain of phosphorylation at M2966 (P = 0.0213);.;.;
MVP		0.34
MPC		0.24
ClinPred		0.47	T
GERP RS		4.7
Varity_R		0.33
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs780927705; hg19: chr3-121396259;