Variant 15-20534564-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145004.2(GOLGA6L6):c.1870G>T(p.Gly624Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 143,718 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 0.000077 ( 0 hom., cov: 40)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L6
NM_001145004.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.67

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05823046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA6L6	NM_001145004.2 linkuse as main transcript	c.1870G>T	p.Gly624Trp	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.1870G>T	p.Gly624Trp	missense_variant	8/9	5	NM_001145004.2	ENSP00000480376.1		A8MZA4

Frequencies

GnomAD3 genomes

AF:

0.0000766

AC:

AN:

143616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000220

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000719

AC:

AN:

1391468

Hom.:

Cov.:

AF XY:

0.00000728

AC XY:

AN XY:

686410

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000745

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000765

AC:

AN:

143718

Hom.:

Cov.:

AF XY:

0.0000855

AC XY:

AN XY:

70208

show subpopulations

Gnomad4 AFR

AF:

0.000215

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000220

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000303

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

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

Apr 04, 2024

The c.1948G>T (p.G650W) 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 1948, causing the glycine (G) at amino acid position 650 to be replaced by a tryptophan (W). 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

0.098

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.038

DANN

Benign

0.19

DEOGEN2

Benign

0.00041

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00054

LIST_S2

Benign

0.049

M_CAP

Benign

0.0071

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.97

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.077

Vest4

0.17

MVP

0.030

ClinPred

0.013

Varity_R

0.041

gMVP

0.0031

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