dbSNP rs1566840695: GOLGA6L6:p.Lys587Glu (chr15-20534675-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_001145004.2(GOLGA6L6):c.1759A>G(p.Lys587Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 921,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.91

Publications

0 publications found

Variant links:

Genes affected

GOLGA6L6 (HGNC:37225): (golgin A6 family like 6)

GOLGA6L6 links:

ENSG00000294965 (HGNC:):

ENSG00000294965 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=0.08298546).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145004.2. 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
	GOLGA6L6	NM_001145004.2	MANE Select	c.1759A>G	p.Lys587Glu	missense	Exon 8 of 9	NP_001138476.2	A8MZA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L6	ENST00000619213.1	TSL:5 MANE Select	c.1759A>G	p.Lys587Glu	missense	Exon 8 of 9	ENSP00000480376.1	A8MZA4
	ENSG00000294965	ENST00000727099.1		n.182+4022T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

112658

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000758

AC:

AN:

131984

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000431

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

AF:

0.00000217

AC:

AN:

921832

Hom.:

Cov.:

AF XY:

0.00000225

AC XY:

AN XY:

445102

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:

20062

American (AMR)

AF:

0.0000612

AC:

AN:

16340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13626

East Asian (EAS)

AF:

0.00

AC:

AN:

7958

South Asian (SAS)

AF:

0.00

AC:

AN:

38210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26754

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2448

European-Non Finnish (NFE)

AF:

0.00000131

AC:

AN:

761098

Other (OTH)

AF:

0.00

AC:

AN:

35336

⚠️ 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

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

112746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55152

African (AFR)

AF:

0.00

AC:

AN:

30564

American (AMR)

AF:

0.00

AC:

AN:

10978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2562

East Asian (EAS)

AF:

0.00

AC:

AN:

3474

South Asian (SAS)

AF:

0.00

AC:

AN:

3526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

232

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50840

Other (OTH)

AF:

0.00

AC:

AN:

1566

Alfa

AF:

0.00

Hom.:

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

0.20

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.3

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.084

M_CAP

Benign

0.0034

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

PhyloP100

-3.9

PrimateAI

Uncertain

0.60

Sift4G

Benign

0.23

Vest4

0.11

MVP

0.014

ClinPred

0.14

Varity_R

0.072

gMVP

0.0016

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over