Genetic Variant GOLGA6L10:p.Glu503Gly (chr15-82342837-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001164465.3(GOLGA6L10):c.1508A>G(p.Glu503Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 53)

Exomes 𝑓: 0.00013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6L10
NM_001164465.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.313

Variant links:

Genes affected

GOLGA6L10 (HGNC:37228): (golgin A6 family like 10)

GOLGA6L10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08502063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6L10	NM_001164465.3 link	c.1508A>G	p.Glu503Gly	missense_variant	Exon 9 of 9	ENST00000610657.2	NP_001157937.2	A6NI86

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6L10	ENST00000610657.2 link	c.1508A>G	p.Glu503Gly	missense_variant	Exon 9 of 9	2	NM_001164465.3	ENSP00000479362.1		A6NI86
GOLGA6L10	ENST00000621197.4 link	c.1259A>G	p.Glu420Gly	missense_variant	Exon 10 of 10	5		ENSP00000484254.2		A0A087X1J3

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000127

AC:

185

AN:

1457406

Hom.:

Cov.:

119

AF XY:

0.000137

AC XY:

AN XY:

725036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000198

Gnomad4 NFE exome

AF:

0.000158

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000123

Hom.:

ExAC

AF:

0.0000184

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1379A>G (p.E460G) alteration is located in exon 9 (coding exon 9) of the GOLGA6L10 gene. This alteration results from a A to G substitution at nucleotide position 1379, causing the glutamic acid (E) at amino acid position 460 to be replaced by a glycine (G). 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

0.079

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

.;.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.36

T;T;T

M_CAP

Benign

0.00057

MetaRNN

Benign

0.085

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.51

Sift4G

Uncertain

0.032

D;T;D

Vest4

0.12

MVP

0.030

ClinPred

0.19

Varity_R

0.076

gMVP

0.074

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