Genetic Variant GOLGA6B:p.Pro291Leu (chr15-72662276-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018652.5(GOLGA6B):c.872C>T(p.Pro291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,386,926 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000044 ( 12 hom. )

Consequence

GOLGA6B
NM_018652.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.383

Variant links:

Genes affected

GOLGA6B (HGNC:32205): (golgin A6 family member B) This gene is found in a large, low copy repeat sequence or duplicon that is found in multiple copies, which are greater than 90% similar, on chromosome 15. Duplicons are associated with deletions, inversions and other chromosomal rearrangements that underlie genomic disease. This gene is a member of the golgin gene family, whose protein products localize to the Golgi apparatus. The majority of the related gene copies are thought to be transcribed pseudogenes. It is not known whether this gene is a pseudogene or if it encodes a golgin protein. [provided by RefSeq, Jul 2008]

GOLGA6B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15825525).

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6B	NM_018652.5 link	c.872C>T	p.Pro291Leu	missense_variant	Exon 11 of 18	ENST00000421285.4	NP_061122.4	A6NDN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6B	ENST00000421285.4 link	c.872C>T	p.Pro291Leu	missense_variant	Exon 11 of 18	1	NM_018652.5	ENSP00000408132.3		A6NDN3

Frequencies

GnomAD3 genomes

AF:

0.0000488

AC:

AN:

123040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000245

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00407

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000107

AC:

AN:

215050

Hom.:

AF XY:

0.0000602

AC XY:

AN XY:

116344

show subpopulations

Gnomad AFR exome

AF:

0.000356

Gnomad AMR exome

AF:

0.000417

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:

0.0000513

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000443

AC:

AN:

1263766

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

626260

show subpopulations

Gnomad4 AFR exome

AF:

0.000323

Gnomad4 AMR exome

AF:

0.000403

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:

0.0000103

Gnomad4 OTH exome

AF:

0.000269

GnomAD4 genome

AF:

0.0000487

AC:

AN:

123160

Hom.:

Cov.:

AF XY:

0.0000506

AC XY:

AN XY:

59330

show subpopulations

Gnomad4 AFR

AF:

0.0000571

Gnomad4 AMR

AF:

0.000245

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000820

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.872C>T (p.P291L) alteration is located in exon 11 (coding exon 11) of the GOLGA6B gene. This alteration results from a C to T substitution at nucleotide position 872, causing the proline (P) at amino acid position 291 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.51

M_CAP

Benign

0.0042

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

2.9

PrimateAI

Pathogenic

0.82

PROVEAN

Pathogenic

-7.2

REVEL

Benign

0.069

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.086

MVP

0.15

ClinPred

0.20

GERP RS

0.69

Varity_R

0.20

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over