1-150694693-A-C

Variant names:

• chr1-150694693-A-C
• rs200411858
• NM_018178.6:c.146T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018178.6(GOLPH3L):​c.146T>G​(p.Met49Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M49T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GOLPH3L NM_018178.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.928

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018178.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLPH3L	NM_018178.6	MANE Select	c.146T>G	p.Met49Arg	missense	Exon 2 of 5	NP_060648.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLPH3L	ENST00000271732.8	TSL:1 MANE Select	c.146T>G	p.Met49Arg	missense	Exon 2 of 5	ENSP00000271732.3	Q9H4A5-1
	GOLPH3L	ENST00000854642.1		c.146T>G	p.Met49Arg	missense	Exon 2 of 5	ENSP00000524701.1
	GOLPH3L	ENST00000854644.1		c.146T>G	p.Met49Arg	missense	Exon 1 of 4	ENSP00000524703.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456740 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724718

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 43574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109914

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.82		Loss of helix (P = 0.0376)
MVP		0.78
MPC		1.2
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.95
gMVP		0.80
Mutation Taster		=34/66	disease causing

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

Other links and lift over

dbSNP: rs200411858; hg19: chr1-150667169;