Genetic Variant NM_001304388.2:c.571T>C (chr15-23443797-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001304388.2(GOLGA6L2):c.571T>C(p.Trp191Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 1,538,416 control chromosomes in the GnomAD database, including 559,609 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.81 ( 50460 hom., cov: 33)

Exomes 𝑓: 0.86 ( 509149 hom. )

Consequence

GOLGA6L2
NM_001304388.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.132

Publications

11 publications found

Variant links:

Genes affected

GOLGA6L2 (HGNC:26695): (golgin A6 family like 2) Predicted to be located in cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

GOLGA6L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2194167E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L2	NM_001304388.2 link	c.571T>C	p.Trp191Arg	missense_variant	Exon 5 of 8	ENST00000567107.6	NP_001291317.1	Q8N9W4-3
GOLGA6L2	XM_047432396.1 link	c.412T>C	p.Trp138Arg	missense_variant	Exon 3 of 6		XP_047288352.1
GOLGA6L2	XM_047432397.1 link	c.571T>C	p.Trp191Arg	missense_variant	Exon 5 of 11		XP_047288353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L2	ENST00000567107.6 link	c.571T>C	p.Trp191Arg	missense_variant	Exon 5 of 8	5	NM_001304388.2	ENSP00000454407.1		Q8N9W4-3
GOLGA6L2	ENST00000566571.5 link	n.541T>C		non_coding_transcript_exon_variant	Exon 4 of 7	5		ENSP00000456523.1		H3BS38

Frequencies

GnomAD3 genomes

AF:

0.808

AC:

122905

AN:

152050

Hom.:

50435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.652

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.867

Gnomad ASJ

AF:

0.848

Gnomad EAS

AF:

0.865

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.903

Gnomad MID

AF:

0.877

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.833

GnomAD2 exomes

AF:

0.849

AC:

123093

AN:

144922

AF XY:

0.849

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.863

Gnomad ASJ exome

AF:

0.843

Gnomad EAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.904

Gnomad NFE exome

AF:

0.865

Gnomad OTH exome

AF:

0.864

GnomAD4 exome

AF:

0.856

AC:

1186717

AN:

1386246

Hom.:

509149

Cov.:

AF XY:

0.856

AC XY:

585598

AN XY:

684288

show subpopulations

African (AFR)

AF:

0.644

AC:

20365

AN:

31646

American (AMR)

AF:

0.867

AC:

31184

AN:

35984

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

21168

AN:

25172

East Asian (EAS)

AF:

0.849

AC:

30480

AN:

35888

South Asian (SAS)

AF:

0.829

AC:

65742

AN:

79336

European-Finnish (FIN)

AF:

0.905

AC:

30979

AN:

34238

Middle Eastern (MID)

AF:

0.854

AC:

4867

AN:

5696

European-Non Finnish (NFE)

AF:

0.864

AC:

932747

AN:

1080138

Other (OTH)

AF:

0.846

AC:

49185

AN:

58148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9092

18184

27275

36367

45459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20856

41712

62568

83424

104280

<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:

0.808

AC:

122978

AN:

152170

Hom.:

50460

Cov.:

AF XY:

0.811

AC XY:

60342

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.651

AC:

27023

AN:

41490

American (AMR)

AF:

0.867

AC:

13265

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.848

AC:

2940

AN:

3466

East Asian (EAS)

AF:

0.865

AC:

4457

AN:

5154

South Asian (SAS)

AF:

0.832

AC:

4013

AN:

4826

European-Finnish (FIN)

AF:

0.903

AC:

9569

AN:

10598

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.866

AC:

58891

AN:

68020

Other (OTH)

AF:

0.836

AC:

1769

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1163

2326

3488

4651

5814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.841

Hom.:

111235

Bravo

AF:

0.798

TwinsUK

AF:

0.870

AC:

3226

ALSPAC

AF:

0.865

AC:

3334

ExAC

AF:

0.800

AC:

72893

Asia WGS

AF:

0.844

AC:

2937

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.4

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0011

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.000050

LIST_S2

Benign

0.023

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PhyloP100

0.13

PrimateAI

Uncertain

0.54

PROVEAN

Benign

2.2

N;.

REVEL

Benign

0.040

Sift4G

Benign

0.33

T;T

Polyphen

0.020

B;.

Vest4

0.092

MutPred

0.42

Gain of disorder (P = 0.0022);.;

MPC

0.015

ClinPred

0.0022

Varity_R

0.11

gMVP

0.089

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over