Genetic Variant GOLPH3L:p.Lys98Arg (chr1-150663654-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_018178.6(GOLPH3L):c.293A>G(p.Lys98Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000954 in 1,613,710 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00097 ( 6 hom. )

Consequence

GOLPH3L
NM_018178.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011252314).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3L	NM_018178.6 link	c.293A>G	p.Lys98Arg	missense_variant	Exon 3 of 5	ENST00000271732.8	NP_060648.2	Q9H4A5-1
GOLPH3L	XM_006711428.3 link	c.335A>G	p.Lys112Arg	missense_variant	Exon 3 of 5		XP_006711491.1
GOLPH3L	XM_047424286.1 link	c.335A>G	p.Lys112Arg	missense_variant	Exon 3 of 5		XP_047280242.1
GOLPH3L	XM_047424285.1 link	c.226-1726A>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.293A>G	p.Lys98Arg	missense_variant	Exon 3 of 5	1	NM_018178.6	ENSP00000271732.3		Q9H4A5-1
GOLPH3L	ENST00000427665.1 link	c.359A>G	p.Lys120Arg	missense_variant	Exon 4 of 6	3		ENSP00000410476.1		Q5T5I6

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00134

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00110

AC:

276

AN:

251066

Hom.:

AF XY:

0.00105

AC XY:

143

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000786

Gnomad NFE exome

AF:

0.00216

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000974

AC:

1424

AN:

1461360

Hom.:

Cov.:

AF XY:

0.000951

AC XY:

691

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000761

AC:

116

AN:

152350

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00134

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.000858

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00178

AC:

216

EpiCase

AF:

0.00109

EpiControl

AF:

0.000712

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.293A>G (p.K98R) 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 293, causing the lysine (K) at amino acid position 98 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.068

DEOGEN2

Benign

0.038

T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.32

N;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.094

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.22

MVP

0.41

MPC

0.24

ClinPred

0.015

GERP RS

4.5

Varity_R

0.059

gMVP

0.26

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