Variant 15-20534506-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145004.2(GOLGA6L6):c.1928C>T(p.Thr643Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,129,454 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00034 ( 18 hom. )

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.74

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012834072).

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2 link	c.1928C>T	p.Thr643Met	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.1928C>T	p.Thr643Met	missense_variant	Exon 8 of 9	5	NM_001145004.2	ENSP00000480376.1		A8MZA4

Frequencies

GnomAD3 genomes

AF:

0.000459

AC:

AN:

37060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000228

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:

0.000702

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000226

AC:

AN:

145878

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

77540

show subpopulations

Gnomad AFR exome

AF:

0.000146

Gnomad AMR exome

AF:

0.0000420

Gnomad ASJ exome

AF:

0.00167

Gnomad EAS exome

AF:

0.000189

Gnomad SAS exome

AF:

0.0000906

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000474

GnomAD4 exome

AF:

0.000341

AC:

372

AN:

1092394

Hom.:

Cov.:

AF XY:

0.000345

AC XY:

183

AN XY:

530248

show subpopulations

Gnomad4 AFR exome

AF:

0.000225

Gnomad4 AMR exome

AF:

0.0000433

Gnomad4 ASJ exome

AF:

0.00215

Gnomad4 EAS exome

AF:

0.0000394

Gnomad4 SAS exome

AF:

0.0000748

Gnomad4 FIN exome

AF:

0.0000713

Gnomad4 NFE exome

AF:

0.000346

Gnomad4 OTH exome

AF:

0.000407

GnomAD4 genome

AF:

0.000459

AC:

AN:

37060

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

18562

show subpopulations

Gnomad4 AFR

AF:

0.000444

Gnomad4 AMR

AF:

0.000228

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000702

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000636

Hom.:

ExAC

AF:

0.000196

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 19, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2006C>T (p.T669M) alteration is located in exon 8 (coding exon 8) of the GOLGA6L6 gene. This alteration results from a C to T substitution at nucleotide position 2006, causing the threonine (T) at amino acid position 669 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.3

DANN

Benign

0.21

DEOGEN2

Benign

0.00058

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00072

LIST_S2

Benign

0.32

M_CAP

Benign

0.0057

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.59

Sift4G

Benign

0.10

Vest4

0.084

MVP

0.014

ClinPred

0.0084

Varity_R

0.024

gMVP

0.0042

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