dbSNP rs4036676: GOLGA8S:p.Leu478Leu (chr15-23364390-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001395373.1(GOLGA8S):c.1434G>T(p.Leu478Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,602,738 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00018 ( 6 hom. )

Consequence

GOLGA8S
NM_001395373.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.14

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:

LOC105370726 (HGNC:):

LOC105370726 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-23364390-G-T is Benign according to our data. Variant chr15-23364390-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644968.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.14 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

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.1434G>T	p.Leu478Leu	synonymous	Exon 16 of 19	NP_001382302.1	H3BPF8
	GOLGA8S	NM_001355465.2		c.756G>T	p.Leu252Leu	synonymous	Exon 15 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.1434G>T	p.Leu478Leu	synonymous	Exon 16 of 19	ENSP00000455298.2	H3BPF8
	GOLGA8S	ENST00000604046.1	TSL:1	n.1769G>T		non_coding_transcript_exon	Exon 15 of 18

Frequencies

GnomAD3 genomes

AF:

0.000468

AC:

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000722

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000665

AC:

AN:

240564

AF XY:

0.0000381

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000276

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000538

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000176

AC:

256

AN:

1450798

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

130

AN XY:

722040

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000299

AC:

AN:

33456

American (AMR)

AF:

0.000112

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26114

East Asian (EAS)

AF:

0.000579

AC:

AN:

39692

South Asian (SAS)

AF:

0.000128

AC:

AN:

85900

European-Finnish (FIN)

AF:

0.000158

AC:

AN:

44440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5450

European-Non Finnish (NFE)

AF:

0.000174

AC:

193

AN:

1110808

Other (OTH)

AF:

0.000249

AC:

AN:

60240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.322

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000467

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74298

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000217

AC:

AN:

41516

American (AMR)

AF:

0.000525

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000775

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000722

AC:

AN:

67878

Other (OTH)

AF:

0.00

AC:

AN:

2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.366

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000336

Hom.:

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.068

(source)

DANN

Benign

0.47

PhyloP100

-1.1

Mutation Taster

=99/1

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