Genetic Variant GOLPH3:p.Asp54Tyr (chr5-32173875-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022130.4(GOLPH3):c.160G>T(p.Asp54Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000262 in 1,527,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

GOLPH3
NM_022130.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

Genes affected

GOLPH3 (HGNC:15452): (golgi phosphoprotein 3) 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 a peripheral membrane protein of the Golgi stack and may have a regulatory role in Golgi trafficking. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined. [provided by RefSeq, Jul 2008]

GOLPH3 links:

GOLPH3-DT (HGNC:55231): (GOLPH3 divergent transcript)

GOLPH3-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
GOLPH3	NM_022130.4 link	c.160G>T	p.Asp54Tyr	missense_variant	Exon 1 of 4	ENST00000265070.7	NP_071413.1	Q9H4A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLPH3	ENST00000265070.7 link	c.160G>T	p.Asp54Tyr	missense_variant	Exon 1 of 4	1	NM_022130.4	ENSP00000265070.6		Q9H4A6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD2 exomes

AF:

0.0000108

AC:

AN:

184464

AF XY:

0.00000966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000218

AC:

AN:

1375344

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

684544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28434

American (AMR)

AF:

0.0000844

AC:

AN:

35546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23598

East Asian (EAS)

AF:

0.00

AC:

AN:

31646

South Asian (SAS)

AF:

0.00

AC:

AN:

77628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5398

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072532

Other (OTH)

AF:

0.00

AC:

AN:

56230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41408

American (AMR)

AF:

0.0000656

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.160G>T (p.D54Y) alteration is located in exon 1 (coding exon 1) of the GOLPH3 gene. This alteration results from a G to T substitution at nucleotide position 160, causing the aspartic acid (D) at amino acid position 54 to be replaced by a tyrosine (Y). 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

Uncertain

0.50

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.49

MetaSVM

Uncertain

-0.13

MutationAssessor

Pathogenic

3.0

PhyloP100

5.0

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.31

MutPred

0.42

Gain of loop (P = 0.0013);

MVP

0.82

MPC

2.3

ClinPred

0.99

GERP RS

4.7

PromoterAI

0.0032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.84

gMVP

0.56

Mutation Taster

=58/42

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr5-32173875-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over