dbSNP rs1595973664: GOLGA6L1:p.Arg520Gly (chr15-23129895-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001413.3(GOLGA6L1):c.1558A>G(p.Arg520Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 147,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000041 ( 0 hom., cov: 37)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L1
NM_001001413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.073650986).

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>G	p.Arg520Gly	missense	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>G	p.Arg520Gly	missense	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes

AF:

0.0000406

AC:

AN:

147606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000205

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000604

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

131102

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000128

AC:

AN:

779618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

402806

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:

61862

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3652

European-Non Finnish (NFE)

AF:

0.00000189

AC:

AN:

529336

Other (OTH)

AF:

0.00

AC:

AN:

36198

⚠️ 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: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000406

AC:

AN:

147606

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

71982

show subpopulations

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

African (AFR)

AF:

0.0000248

AC:

AN:

40380

American (AMR)

AF:

0.00

AC:

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.000205

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:

0.0000604

AC:

AN:

66198

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 = 0.0153586), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.367

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

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

CADD

Benign

4.6

(source)

DANN

Benign

0.22

DEOGEN2

Benign

0.032

LIST_S2

Benign

0.30

MetaRNN

Benign

0.074

PhyloP100

-1.3

Sift4G

Uncertain

0.055

Vest4

0.15

gMVP

0.018

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