Genetic Variant GOLGA6L1:p.Arg520Arg (chr15-23129895-T-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001001413.3(GOLGA6L1):c.1558A>C(p.Arg520Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 147,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 37)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L1
NM_001001413.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

0 publications found

Variant links:

Genes affected

GOLGA6L1 (HGNC:37444): (golgin A6 family like 1)

GOLGA6L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (Cadd=4.991).

BP7

Synonymous conserved (PhyloP=-1.26 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001413.3. 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
	GOLGA6L1	NM_001001413.3	MANE Select	c.1558A>C	p.Arg520Arg	synonymous	Exon 8 of 9	NP_001001413.3	Q8N7Z2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L1	ENST00000614055.2	TSL:5 MANE Select	c.1558A>C	p.Arg520Arg	synonymous	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000513

AC:

AN:

779592

Hom.:

Cov.:

AF XY:

0.00000745

AC XY:

AN XY:

402802

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

22008

American (AMR)

AF:

0.00

AC:

AN:

31430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19944

East Asian (EAS)

AF:

0.00

AC:

AN:

30220

South Asian (SAS)

AF:

0.00

AC:

AN:

61864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3652

European-Non Finnish (NFE)

AF:

0.00000756

AC:

AN:

529316

Other (OTH)

AF:

0.00

AC:

AN:

36190

⚠️ 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: 0.263

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147610

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71980

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

40386

American (AMR)

AF:

0.00

AC:

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

4870

South Asian (SAS)

AF:

0.00

AC:

AN:

4436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66194

Other (OTH)

AF:

0.00

AC:

AN:

2034

⚠️ 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: 0.275

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

CADD

Benign

5.0

(source)

DANN

Benign

0.27

PhyloP100

-1.3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over