1-150648565-T-C

Variant names:

• chr1-150648565-T-C
• rs371107154
• NM_018178.6:c.614A>G

Variant summary

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

The NM_018178.6(GOLPH3L):​c.614A>G​(p.Asp205Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GOLPH3L NM_018178.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84

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 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	c.614A>G	p.Asp205Gly	missense_variant	Exon 5 of 5	ENST00000271732.8	NP_060648.2
GOLPH3L	XM_006711428.3	c.656A>G	p.Asp219Gly	missense_variant	Exon 5 of 5		XP_006711491.1
GOLPH3L	XM_047424285.1	c.524A>G	p.Asp175Gly	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.614A>G	p.Asp205Gly	missense_variant	Exon 5 of 5	1	NM_018178.6	ENSP00000271732.3
GOLPH3L	ENST00000427665.1	c.680A>G	p.Asp227Gly	missense_variant	Exon 6 of 6	3		ENSP00000410476.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461742 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.614A>G (p.D205G) 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 614, causing the aspartic acid (D) at amino acid position 205 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	Benign	0.24
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.0041	T
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Uncertain	0.38
Sift	Benign	0.16	T;T
Sift4G	Benign	0.19	T;.
Polyphen		0.0	B;.
Vest4		0.17
MVP		0.66
MPC		0.39
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs371107154; hg19: chr1-150621041;