Genetic Variant GOLPH3L:p.Asp103Gly (chr1-150663639-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018178.6(GOLPH3L):c.308A>G(p.Asp103Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GOLPH3L
NM_018178.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

Genes affected

GOLPH3L (HGNC:24882): (golgi phosphoprotein 3 like) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is localized at the Golgi stack and may have a regulatory role in Golgi trafficking. [provided by RefSeq, Jul 2008]

GOLPH3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2715766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3L	NM_018178.6 link	c.308A>G	p.Asp103Gly	missense_variant	Exon 3 of 5	ENST00000271732.8	NP_060648.2	Q9H4A5-1
GOLPH3L	XM_006711428.3 link	c.350A>G	p.Asp117Gly	missense_variant	Exon 3 of 5		XP_006711491.1
GOLPH3L	XM_047424286.1 link	c.350A>G	p.Asp117Gly	missense_variant	Exon 3 of 5		XP_047280242.1
GOLPH3L	XM_047424285.1 link	c.226-1711A>G		intron_variant	Intron 2 of 3		XP_047280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLPH3L	ENST00000271732.8 link	c.308A>G	p.Asp103Gly	missense_variant	Exon 3 of 5	1	NM_018178.6	ENSP00000271732.3		Q9H4A5-1
GOLPH3L	ENST00000427665.1 link	c.374A>G	p.Asp125Gly	missense_variant	Exon 4 of 6	3		ENSP00000410476.1		Q5T5I6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.308A>G (p.D103G) alteration is located in exon 3 (coding exon 2) of the GOLPH3L gene. This alteration results from a A to G substitution at nucleotide position 308, causing the aspartic acid (D) at amino acid position 103 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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.0038

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.024

D;T

Sift4G

Uncertain

0.053

T;.

Polyphen

0.071

B;.

Vest4

0.45

MutPred

0.39

Loss of stability (P = 0.0425);.;

MVP

0.51

MPC

0.38

ClinPred

0.68

GERP RS

4.5

Varity_R

0.20

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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