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

Variant summary

Our verdict is Likely benign. The variant received -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. 9/14 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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2644967.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395373.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8S	NM_001395373.1	MANE Select	c.818C>T	p.Ser273Leu	missense	Exon 10 of 19	NP_001382302.1	H3BPF8
	GOLGA8S	NM_001355465.2		c.140C>T	p.Ser47Leu	missense	Exon 9 of 18	NP_001342394.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8S	ENST00000562295.3	TSL:5 MANE Select	c.818C>T	p.Ser273Leu	missense	Exon 10 of 19	ENSP00000455298.2	H3BPF8
	GOLGA8S	ENST00000604046.1	TSL:1	n.1153C>T		non_coding_transcript_exon	Exon 9 of 18

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

685

AN:

147838

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00457

AC:

298

AN:

65178

AF XY:

0.00464

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 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

African (AFR)

AF:

0.000822

AC:

AN:

18254

American (AMR)

AF:

0.00249

AC:

107

AN:

43058

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

202

AN:

20604

East Asian (EAS)

AF:

0.0000828

AC:

AN:

36218

South Asian (SAS)

AF:

0.000394

AC:

AN:

68510

European-Finnish (FIN)

AF:

0.00487

AC:

242

AN:

49718

Middle Eastern (MID)

AF:

0.00348

AC:

AN:

2586

European-Non Finnish (NFE)

AF:

0.00759

AC:

3000

AN:

395448

Other (OTH)

AF:

0.00546

AC:

187

AN:

34226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.00126

AC:

AN:

39840

American (AMR)

AF:

0.00250

AC:

AN:

14826

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3388

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.000226

AC:

AN:

4422

European-Finnish (FIN)

AF:

0.00498

AC:

AN:

10440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00752

AC:

502

AN:

66792

Other (OTH)

AF:

0.00294

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00157

Hom.:

ExAC

AF:

0.00121

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.97

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.78

M_CAP

Benign

0.00083

MetaRNN

Benign

0.0070

PhyloP100

1.5

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

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over