Genetic Variant GOLGA8S:p.Ser273Leu (chr15-23360525-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001395373.1(GOLGA8S):c.818C>T(p.Ser273Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 27 hom., cov: 27)

Exomes 𝑓: 0.0057 ( 95 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8S
NM_001395373.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069929957).

BP6

Variant 15-23360525-C-T is Benign according to our data. Variant chr15-23360525-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644967.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8S	NM_001395373.1 link	c.818C>T	p.Ser273Leu	missense_variant	Exon 10 of 19	ENST00000562295.3	NP_001382302.1
GOLGA8S	NM_001355465.2 link	c.140C>T	p.Ser47Leu	missense_variant	Exon 9 of 18		NP_001342394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA8S	ENST00000562295.3 link	c.818C>T	p.Ser273Leu	missense_variant	Exon 10 of 19	5	NM_001395373.1	ENSP00000455298.2		H3BPF8
GOLGA8S	ENST00000604046.1 link	n.1153C>T		non_coding_transcript_exon_variant	Exon 9 of 18	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

685

AN:

147838

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00250

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000226

Gnomad FIN

AF:

0.00498

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00749

Gnomad OTH

AF:

0.00298

GnomAD3 exomes

AF:

0.00457

AC:

298

AN:

65178

Hom.:

AF XY:

0.00464

AC XY:

150

AN XY:

32310

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000160

Gnomad FIN exome

AF:

0.00496

Gnomad NFE exome

AF:

0.00760

Gnomad OTH exome

AF:

0.00809

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00567

AC:

3792

AN:

668622

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

2030

AN XY:

360646

show subpopulations

Gnomad4 AFR exome

AF:

0.000822

Gnomad4 AMR exome

AF:

0.00249

Gnomad4 ASJ exome

AF:

0.00980

Gnomad4 EAS exome

AF:

0.0000828

Gnomad4 SAS exome

AF:

0.000394

Gnomad4 FIN exome

AF:

0.00487

Gnomad4 NFE exome

AF:

0.00759

Gnomad4 OTH exome

AF:

0.00546

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00464

AC:

687

AN:

147958

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

322

AN XY:

72096

show subpopulations

Gnomad4 AFR

AF:

0.00126

Gnomad4 AMR

AF:

0.00250

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000226

Gnomad4 FIN

AF:

0.00498

Gnomad4 NFE

AF:

0.00752

Gnomad4 OTH

AF:

0.00294

Alfa

AF:

0.00157

Hom.:

ExAC

AF:

0.00121

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GOLGA8S: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.78

M_CAP

Benign

0.00083

MetaRNN

Benign

0.0070

PROVEAN

Uncertain

-3.8

Sift

Benign

0.12

Sift4G

Benign

0.22

Vest4

0.17

MVP

0.32

MPC

1.6

GERP RS

-0.15

Varity_R

0.092

gMVP

0.13

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

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