dbSNP rs1380404004: GOLGA6L6:p.Glu662Gln (chr15-20534450-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001145004.2(GOLGA6L6):c.1984G>C(p.Glu662Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,304,074 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E662K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.30

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10497594).

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.1984G>C	p.Glu662Gln	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.1984G>C	p.Glu662Gln	missense	Exon 8 of 9	ENSP00000480376.1	A8MZA4
	ENSG00000294965	ENST00000727099.1		n.182+3797C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000737

AC:

AN:

135722

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:

0.000206

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

GnomAD4 exome

AF:

0.00000690

AC:

AN:

1304074

Hom.:

Cov.:

AF XY:

0.00000777

AC XY:

AN XY:

643742

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:

27668

American (AMR)

AF:

0.00

AC:

AN:

30862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23312

East Asian (EAS)

AF:

0.000292

AC:

AN:

30776

South Asian (SAS)

AF:

0.00

AC:

AN:

72184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4086

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1019020

Other (OTH)

AF:

0.00

AC:

AN:

53582

⚠️ 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: 0.292

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: AS_VQSR

AF:

0.00000736

AC:

AN:

135828

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

66322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

35008

American (AMR)

AF:

0.00

AC:

AN:

13694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3238

East Asian (EAS)

AF:

0.000207

AC:

AN:

4832

South Asian (SAS)

AF:

0.00

AC:

AN:

4134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62504

Other (OTH)

AF:

0.00

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.049

Eigen

Benign

-0.75

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.46

M_CAP

Benign

0.0017

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PhyloP100

-2.3

PrimateAI

Uncertain

0.58

Sift4G

Benign

0.14

Vest4

0.070

MVP

0.055

ClinPred

0.20

Varity_R

0.048

gMVP

0.0065

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over