Genetic Variant GOLGA6L1:p.Asp506Asn (chr15-23129937-C-T) – 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_001001413.3(GOLGA6L1):c.1516G>A(p.Asp506Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000036 ( 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: -4.08

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09356475).

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.1516G>A	p.Asp506Asn	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.1516G>A	p.Asp506Asn	missense	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes

AF:

0.0000173

AC:

AN:

115604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000316

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:

0.0000184

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000361

AC:

AN:

553798

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

294698

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:

15902

American (AMR)

AF:

0.00

AC:

AN:

27650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17284

East Asian (EAS)

AF:

0.00

AC:

AN:

28062

South Asian (SAS)

AF:

0.0000182

AC:

AN:

55052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35224

Middle Eastern (MID)

AF:

0.000420

AC:

AN:

2382

European-Non Finnish (NFE)

AF:

0.0000494

AC:

AN:

344220

Other (OTH)

AF:

0.0000357

AC:

AN:

28022

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000111022), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.307

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

AF:

0.0000173

AC:

AN:

115604

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

55570

show subpopulations

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

African (AFR)

AF:

0.0000316

AC:

AN:

31674

American (AMR)

AF:

0.00

AC:

AN:

11534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2926

East Asian (EAS)

AF:

0.00

AC:

AN:

3118

South Asian (SAS)

AF:

0.00

AC:

AN:

2812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.0000184

AC:

AN:

54232

Other (OTH)

AF:

0.00

AC:

AN:

1566

⚠️ 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: 0.300

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000103

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

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.2

(source)

DANN

Benign

0.47

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.72

M_CAP

Benign

0.0035

MetaRNN

Benign

0.094

PhyloP100

-4.1

Sift4G

Benign

0.12

Vest4

0.13

MVP

0.040

GERP RS

0.15

Varity_R

0.048

gMVP

0.0058

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