rs139068177

Variant names:

• chr15-44328732-C-T
• rs139068177
• NM_138423.4:c.430C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_138423.4(GOLM2):​c.430C>T​(p.Leu144Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3189383).

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.430C>T	p.Leu144Phe	missense	Exon 3 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.430C>T	p.Leu144Phe	missense	Exon 3 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.741C>T		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.430C>T	p.Leu144Phe	missense	Exon 3 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.430C>T	p.Leu144Phe	missense	Exon 3 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000557945.5	TSL:1	n.430C>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000453720.1	Q6P4E1-3

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152162 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 250434 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000500 AC: 73 AN: 1460958 Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29 AN XY: 726756

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.0000449 AC: 2 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.0000639 AC: 71 AN: 1111676

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152162 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74334

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.000327 AC: 5 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.47
MVP		0.79
MPC		0.48
ClinPred		0.80	D
GERP RS		5.0
gMVP		0.16
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs139068177; hg19: chr15-44620930;