NM_138423.4:c.470G>A

Variant names:

• chr15-44328772-G-A
• NM_138423.4:c.470G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138423.4(GOLM2):​c.470G>A​(p.Arg157Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.20

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19411346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLM2	NM_138423.4	c.470G>A	p.Arg157Lys	missense_variant	Exon 3 of 10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3	c.470G>A	p.Arg157Lys	missense_variant	Exon 3 of 9		NP_816929.1
GOLM2	NR_157849.2	n.781G>A		non_coding_transcript_exon_variant	Exon 3 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLM2	ENST00000299957.11	c.470G>A	p.Arg157Lys	missense_variant	Exon 3 of 10	1	NM_138423.4	ENSP00000299957.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Benign	0.71
DEOGEN2	Benign	0.0081	T;.;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.49	.;N;.;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.27	N;N;.;N
REVEL	Uncertain	0.30
Sift	Benign	0.37	T;T;.;T
Sift4G	Benign	0.096	T;T;.;T
Polyphen		0.94	.;.;.;P
Vest4		0.30, 0.34
MutPred		0.25		.;Gain of methylation at R157 (P = 0.0172);.;Gain of methylation at R157 (P = 0.0172);
MVP		0.77
MPC		0.43
ClinPred		0.62	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.050

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: chr15-44620970;