Genetic Variant GOLPH3L:p.Cys70Trp (chr1-150663737-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018178.6(GOLPH3L):c.210C>G(p.Cys70Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GOLPH3L
NM_018178.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3L	NM_018178.6 link	c.210C>G	p.Cys70Trp	missense_variant	Exon 3 of 5	ENST00000271732.8	NP_060648.2	Q9H4A5-1
GOLPH3L	XM_006711428.3 link	c.252C>G	p.Cys84Trp	missense_variant	Exon 3 of 5		XP_006711491.1
GOLPH3L	XM_047424286.1 link	c.252C>G	p.Cys84Trp	missense_variant	Exon 3 of 5		XP_047280242.1
GOLPH3L	XM_047424285.1 link	c.226-1809C>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.210C>G	p.Cys70Trp	missense_variant	Exon 3 of 5	1	NM_018178.6	ENSP00000271732.3		Q9H4A5-1
GOLPH3L	ENST00000427665.1 link	c.276C>G	p.Cys92Trp	missense_variant	Exon 4 of 6	3		ENSP00000410476.1		Q5T5I6

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251314

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460968

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726854

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0000895

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:

0.000217

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000196

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:

0.000302

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.210C>G (p.C70W) alteration is located in exon 3 (coding exon 2) of the GOLPH3L gene. This alteration results from a C to G substitution at nucleotide position 210, causing the cysteine (C) at amino acid position 70 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

T;T

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-8.8

D;D

REVEL

Pathogenic

0.80

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.050

T;.

Polyphen

1.0

D;.

Vest4

0.88

MVP

0.60

MPC

0.67

ClinPred

0.29

GERP RS

1.6

Varity_R

0.67

gMVP

0.67

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