NM_138423.4:c.862C>T

Variant names:

• chr15-44379749-C-T
• NM_138423.4:c.862C>T

Variant summary

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

The NM_138423.4(GOLM2):​c.862C>T​(p.Leu288Phe) 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. 13/19 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: 0.220

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=0.12427449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLM2	NM_138423.4	c.862C>T	p.Leu288Phe	missense_variant	Exon 7 of 10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3	c.862C>T	p.Leu288Phe	missense_variant	Exon 7 of 9		NP_816929.1
GOLM2	NR_157849.2	n.2565C>T		non_coding_transcript_exon_variant	Exon 8 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLM2	ENST00000299957.11	c.862C>T	p.Leu288Phe	missense_variant	Exon 7 of 10	1	NM_138423.4	ENSP00000299957.6
GOLM2	ENST00000345795.6	c.862C>T	p.Leu288Phe	missense_variant	Exon 7 of 9	1		ENSP00000335063.4
GOLM2	ENST00000650436.1	c.505C>T	p.Leu169Phe	missense_variant	Exon 9 of 12			ENSP00000496905.1
GOLM2	ENST00000558847.1	c.202C>T	p.Leu68Phe	missense_variant	Exon 2 of 4	3		ENSP00000453465.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;.;N
REVEL	Benign	0.047
Sift	Benign	0.28	T;.;T
Sift4G	Benign	0.30	T;.;T
Polyphen		0.37	.;.;B
Vest4		0.17
MutPred		0.23		Loss of glycosylation at T290 (P = 0.0912);.;Loss of glycosylation at T290 (P = 0.0912);
MVP		0.26
MPC		0.59
ClinPred		0.14	T
GERP RS		0.85
gMVP		0.19

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: chr15-44671947;