15-44380854-C-G

Variant names:

• chr15-44380854-C-G
• rs150204732
• NM_138423.4:c.950C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138423.4(GOLM2):​c.950C>G​(p.Pro317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. P317L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 0 publications found

Genes affected

GOLM2 (HGNC:24892): (golgi membrane protein 2) The increased expression level of this gene is associated with HER-2/neu proto-oncogene overexpression. Amplification and resulting overexpression of this proto-oncogene are found in approximately 30% of human breast and 20% of human ovarian cancers. Alternatively spliced variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28240094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138423.4. 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
	GOLM2	NM_138423.4	MANE Select	c.950C>G	p.Pro317Arg	missense	Exon 8 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.950C>G	p.Pro317Arg	missense	Exon 8 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.2653C>G		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.950C>G	p.Pro317Arg	missense	Exon 8 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.950C>G	p.Pro317Arg	missense	Exon 8 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000915850.1		c.935C>G	p.Pro312Arg	missense	Exon 8 of 10	ENSP00000585909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435558 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 713428

African (AFR) AF: 0.00 AC: 0 AN: 32806

American (AMR) AF: 0.00 AC: 0 AN: 42402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25586

East Asian (EAS) AF: 0.00 AC: 0 AN: 38710

South Asian (SAS) AF: 0.00 AC: 0 AN: 80144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1098484

Other (OTH) AF: 0.00 AC: 0 AN: 59170

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.0
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.21		Loss of glycosylation at P317 (P = 0.0076)
MVP		0.41
MPC		1.1
ClinPred		0.97	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.37

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: rs150204732; hg19: chr15-44673052;