1-150648652-T-C

Variant names:

• chr1-150648652-T-C
• NM_018178.6:c.527A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018178.6(GOLPH3L):​c.527A>G​(p.Glu176Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLPH3L NM_018178.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.94

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3L	NM_018178.6	c.527A>G	p.Glu176Gly	missense_variant	Exon 5 of 5	ENST00000271732.8	NP_060648.2
GOLPH3L	XM_006711428.3	c.569A>G	p.Glu190Gly	missense_variant	Exon 5 of 5		XP_006711491.1
GOLPH3L	XM_047424285.1	c.437A>G	p.Glu146Gly	missense_variant	Exon 4 of 4		XP_047280241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLPH3L	ENST00000271732.8	c.527A>G	p.Glu176Gly	missense_variant	Exon 5 of 5	1	NM_018178.6	ENSP00000271732.3
GOLPH3L	ENST00000427665.1	c.593A>G	p.Glu198Gly	missense_variant	Exon 6 of 6	3		ENSP00000410476.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.527A>G (p.E176G) alteration is located in exon 5 (coding exon 4) of the GOLPH3L gene. This alteration results from a A to G substitution at nucleotide position 527, causing the glutamic acid (E) at amino acid position 176 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	0.76
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.0077	T
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.28
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.049	D;.
Polyphen		0.0040	B;.
Vest4		0.46
MutPred		0.69		Gain of sheet (P = 0.0344);.;
MVP		0.64
MPC		0.56
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.40
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-150621128;