rs150623963

Variant names:

• chr1-150663684-C-G
• rs150623963
• NM_018178.6:c.263G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-150663684-C-G
• chr1-150663684-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018178.6(GOLPH3L):​c.263G>C​(p.Arg88Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R88Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLPH3L NM_018178.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.79

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLPH3L	NM_018178.6	c.263G>C	p.Arg88Pro	missense_variant	Exon 3 of 5	ENST00000271732.8	NP_060648.2
GOLPH3L	XM_006711428.3	c.305G>C	p.Arg102Pro	missense_variant	Exon 3 of 5		XP_006711491.1
GOLPH3L	XM_047424286.1	c.305G>C	p.Arg102Pro	missense_variant	Exon 3 of 5		XP_047280242.1
GOLPH3L	XM_047424285.1	c.226-1756G>C		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	c.263G>C	p.Arg88Pro	missense_variant	Exon 3 of 5	1	NM_018178.6	ENSP00000271732.3
GOLPH3L	ENST00000427665.1	c.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 6	3		ENSP00000410476.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Pathogenic	2.9	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0050	D;.
Polyphen		1.0	D;.
Vest4		0.98
MutPred		0.82		Loss of MoRF binding (P = 0.042);.;
MVP		0.76
MPC		1.2
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.90
gMVP		0.90

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

Other links and lift over

dbSNP: rs150623963; hg19: chr1-150636160;