Genetic Variant GOLGA6L1:p.Cys623Gly (chr15-23129586-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001001413.3(GOLGA6L1):c.1867T>G(p.Cys623Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/12 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. C623R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000085 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L1
NM_001001413.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055083483).

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.1867T>G	p.Cys623Gly	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.1867T>G	p.Cys623Gly	missense	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes

AF:

0.00000850

AC:

AN:

117660

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:

0.000310

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:

0.000404

AC:

AN:

96594

AF XY:

0.000325

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000927

Gnomad ASJ exome

AF:

0.000370

Gnomad EAS exome

AF:

0.000567

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000218

AC:

AN:

457898

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

243048

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:

12704

American (AMR)

AF:

0.00

AC:

AN:

20696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13960

East Asian (EAS)

AF:

0.00

AC:

AN:

31150

South Asian (SAS)

AF:

0.00

AC:

AN:

46046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2006

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

274740

Other (OTH)

AF:

0.0000379

AC:

AN:

26414

⚠️ 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: 0.275

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:

0.00000849

AC:

AN:

117766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

56816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32588

American (AMR)

AF:

0.00

AC:

AN:

11810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2982

East Asian (EAS)

AF:

0.000311

AC:

AN:

3220

South Asian (SAS)

AF:

0.00

AC:

AN:

2802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

54158

Other (OTH)

AF:

0.00

AC:

AN:

1532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

0.080

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.78

(source)

DANN

Benign

0.26

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.19

M_CAP

Benign

0.0030

MetaRNN

Benign

0.055

PhyloP100

-1.9

Sift4G

Benign

0.40

Vest4

0.11

MVP

0.22

Varity_R

0.069

gMVP

0.016

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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