Genetic Variant GOLGA8S:p.Ile498Thr (chr15-23364531-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395373.1(GOLGA8S):c.1493T>C(p.Ile498Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,587,840 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 10 hom., cov: 27)

Exomes 𝑓: 0.0045 ( 123 hom. )

Consequence

GOLGA8S
NM_001395373.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.88

Variant links:

Genes affected

GOLGA8S (HGNC:44409): (golgin A8 family member S) Predicted to be involved in Golgi organization. Predicted to be active in Golgi cis cisterna; Golgi cisterna membrane; and cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

GOLGA8S links:

LOC105370726 (HGNC:):

LOC105370726 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008637726).

BP6

Variant 15-23364531-T-C is Benign according to our data. Variant chr15-23364531-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3770700.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
GOLGA8S	NM_001395373.1 link	c.1493T>C	p.Ile498Thr	missense_variant	Exon 17 of 19	ENST00000562295.3	NP_001382302.1
GOLGA8S	NM_001355465.2 link	c.815T>C	p.Ile272Thr	missense_variant	Exon 16 of 18		NP_001342394.1
LOC105370726	XR_931975.3 link	n.90-171A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA8S	ENST00000562295.3 link	c.1493T>C	p.Ile498Thr	missense_variant	Exon 17 of 19	5	NM_001395373.1	ENSP00000455298.2		H3BPF8
GOLGA8S	ENST00000604046.1 link	n.1828T>C		non_coding_transcript_exon_variant	Exon 16 of 18	1

Frequencies

GnomAD3 genomes

AF:

0.00980

AC:

1460

AN:

149052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00895

Gnomad ASJ

AF:

0.0111

Gnomad EAS

AF:

0.00375

Gnomad SAS

AF:

0.00957

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00781

GnomAD3 exomes

AF:

0.00798

AC:

1836

AN:

229980

Hom.:

AF XY:

0.00788

AC XY:

995

AN XY:

126312

show subpopulations

Gnomad AFR exome

AF:

0.00820

Gnomad AMR exome

AF:

0.00602

Gnomad ASJ exome

AF:

0.00809

Gnomad EAS exome

AF:

0.00241

Gnomad SAS exome

AF:

0.00765

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.00894

Gnomad OTH exome

AF:

0.00856

GnomAD4 exome

AF:

0.00452

AC:

6506

AN:

1438666

Hom.:

123

Cov.:

AF XY:

0.00479

AC XY:

3432

AN XY:

716062

show subpopulations

Gnomad4 AFR exome

AF:

0.00463

Gnomad4 AMR exome

AF:

0.00513

Gnomad4 ASJ exome

AF:

0.00863

Gnomad4 EAS exome

AF:

0.00119

Gnomad4 SAS exome

AF:

0.00642

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.00390

Gnomad4 OTH exome

AF:

0.00547

GnomAD4 genome

AF:

0.00980

AC:

1462

AN:

149174

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

739

AN XY:

72826

show subpopulations

Gnomad4 AFR

AF:

0.00753

Gnomad4 AMR

AF:

0.00894

Gnomad4 ASJ

AF:

0.0111

Gnomad4 EAS

AF:

0.00376

Gnomad4 SAS

AF:

0.00957

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00773

Alfa

AF:

0.00674

Hom.:

ExAC

AF:

0.00950

AC:

1111

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GOLGA8S: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.2

DANN

Benign

0.38

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0086

PROVEAN

Benign

-0.040

Sift

Benign

0.19

Sift4G

Benign

0.43

Vest4

0.17

MVP

0.55

MPC

1.8

GERP RS

0.83

Varity_R

0.025

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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