Variant 15-20534587-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_001145004.2(GOLGA6L6):c.1847C>T(p.Thr616Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0302 in 97,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0039 ( 8 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.18

Variant links:

Genes affected

GOLGA6L6 (HGNC:37225): (golgin A6 family like 6)

GOLGA6L6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Variant has high frequency in the AFR(0.00867279) population. However there is too low homozygotes in high coverage region: (expected more than 22, got 0).

BP4

Computational evidence support a benign effect (MetaRNN=0.0030660033).

BP6

Variant 15-20534587-G-A is Benign according to our data. Variant chr15-20534587-G-A is described in ClinVar as [Benign]. Clinvar id is 402906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0302 (2941/97252) while in subpopulation AFR AF= 0.0425 (995/23426). AF 95% confidence interval is 0.0403. There are 0 homozygotes in gnomad4. There are 1382 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2 link	c.1847C>T	p.Thr616Met	missense_variant	Exon 8 of 9	ENST00000619213.1	NP_001138476.2	A8MZA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1 link	c.1847C>T	p.Thr616Met	missense_variant	Exon 8 of 9	5	NM_001145004.2	ENSP00000480376.1		A8MZA4

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

2945

AN:

97150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0427

Gnomad AMI

AF:

0.0115

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0177

Gnomad EAS

AF:

0.00129

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.0362

Gnomad NFE

AF:

0.0307

Gnomad OTH

AF:

0.0302

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00387

AC:

4674

AN:

1208304

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2242

AN XY:

595844

show subpopulations

Gnomad4 AFR exome

AF:

0.00965

Gnomad4 AMR exome

AF:

0.00350

Gnomad4 ASJ exome

AF:

0.00273

Gnomad4 EAS exome

AF:

0.0000883

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00605

Gnomad4 NFE exome

AF:

0.00396

Gnomad4 OTH exome

AF:

0.00430

GnomAD4 genome

AF:

0.0302

AC:

2941

AN:

97252

Hom.:

Cov.:

AF XY:

0.0290

AC XY:

1382

AN XY:

47672

show subpopulations

Gnomad4 AFR

AF:

0.0425

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.0177

Gnomad4 EAS

AF:

0.00130

Gnomad4 SAS

AF:

0.0179

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.0306

Gnomad4 OTH

AF:

0.0299

Alfa

AF:

0.0570

Hom.:

ExAC

AF:

0.0675

AC:

1379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.24

DANN

Benign

0.22

DEOGEN2

Benign

0.00060

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00091

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.56

Sift4G

Benign

0.22

Vest4

0.035

ClinPred

0.016

Varity_R

0.015

gMVP

0.0038

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over