dbSNP rs1374626047: GOLGA6L1:p.Trp519Arg (chr15-23129898-A-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.1555T>A(p.Trp519Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000027 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000066 ( 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: -2.92

Publications

3 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=0.11564565).

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.1555T>A	p.Trp519Arg	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.1555T>A	p.Trp519Arg	missense	Exon 8 of 9	ENSP00000478478.1	Q8N7Z2

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000320

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000197

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000664

AC:

AN:

753322

Hom.:

Cov.:

AF XY:

0.00000256

AC XY:

AN XY:

389998

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:

21464

American (AMR)

AF:

0.00

AC:

AN:

30578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19576

East Asian (EAS)

AF:

0.00

AC:

AN:

29088

South Asian (SAS)

AF:

0.00

AC:

AN:

60152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3552

European-Non Finnish (NFE)

AF:

0.00000982

AC:

AN:

509306

Other (OTH)

AF:

0.00

AC:

AN:

35242

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000303018), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.285

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000267

AC:

AN:

112418

Hom.:

Cov.:

AF XY:

0.0000182

AC XY:

AN XY:

55062

show subpopulations

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

African (AFR)

AF:

0.0000320

AC:

AN:

31254

American (AMR)

AF:

0.00

AC:

AN:

11622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2780

East Asian (EAS)

AF:

0.00

AC:

AN:

3230

South Asian (SAS)

AF:

0.000319

AC:

AN:

3136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

158

European-Non Finnish (NFE)

AF:

0.0000197

AC:

AN:

50716

Other (OTH)

AF:

0.00

AC:

AN:

1554

⚠️ 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: 0.275

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

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

0.32

CADD

Benign

5.0

(source)

DANN

Benign

0.34

LIST_S2

Benign

0.021

MetaRNN

Benign

0.12

PhyloP100

-2.9

Sift4G

Benign

0.41

Vest4

0.11

gMVP

0.015

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