Variant 15-20534565-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145004.2(GOLGA6L6):c.1869G>T(p.Met623Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000603 in 149,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000060 ( 0 hom., cov: 40)

Exomes 𝑓: 0.000098 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.54

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058870494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2 linkuse as main transcript	c.1869G>T	p.Met623Ile	missense_variant	8/9	ENST00000619213.1	NP_001138476.2	A8MZA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA6L6	ENST00000619213.1 linkuse as main transcript	c.1869G>T	p.Met623Ile	missense_variant	8/9	5	NM_001145004.2	ENSP00000480376.1		A8MZA4

Frequencies

GnomAD3 genomes

AF:

0.0000603

AC:

AN:

149332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

143948

Hom.:

AF XY:

0.0000649

AC XY:

AN XY:

77044

show subpopulations

Gnomad AFR exome

AF:

0.000149

Gnomad AMR exome

AF:

0.0000830

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000254

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000977

AC:

136

AN:

1392596

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

686938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000322

Gnomad4 AMR exome

AF:

0.0000281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.0000867

GnomAD4 genome

AF:

0.0000603

AC:

AN:

149332

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

72952

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000104

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000962

Hom.:

ExAC

AF:

0.0000459

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2021

The c.1947G>T (p.M649I) alteration is located in exon 8 (coding exon 8) of the GOLGA6L6 gene. This alteration results from a G to T substitution at nucleotide position 1947, causing the methionine (M) at amino acid position 649 to be replaced by an isoleucine (I). 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

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.11

DANN

Benign

0.32

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0081

LIST_S2

Benign

0.52

M_CAP

Benign

0.0023

MetaRNN

Benign

0.059

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

Sift4G

Benign

0.53

Vest4

0.096

MVP

0.030

ClinPred

0.0066

Varity_R

0.081

gMVP

0.0054

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