rs371987081

Variant names:

• chr15-44338300-T-G
• rs371987081
• NM_138423.4:c.785T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-44338300-T-G
• chr15-44338300-T-A
• chr15-44338300-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138423.4(GOLM2):​c.785T>G​(p.Val262Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,613,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.22
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01922977).

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.785T>G	p.Val262Gly	missense	Exon 6 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.785T>G	p.Val262Gly	missense	Exon 6 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.1096T>G		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.785T>G	p.Val262Gly	missense	Exon 6 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.785T>G	p.Val262Gly	missense	Exon 6 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000557945.5	TSL:1	n.*160T>G		non_coding_transcript_exon	Exon 5 of 6	ENSP00000453720.1	Q6P4E1-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000127 AC: 32 AN: 251226 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000623 AC: 91 AN: 1461056 Hom.: 0 Cov.: 30 AF XY: 0.0000784 AC XY: 57 AN XY: 726862

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.000731 AC: 63 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111388

Other (OTH) AF: 0.000133 AC: 8 AN: 60360

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000681 Hom.: 0

Bravo AF: 0.0000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	3.7
DANN	Uncertain	0.98
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.034	B
Vest4		0.21
MVP		0.37
MPC		0.56
ClinPred		0.060	T
GERP RS		-6.3
gMVP		0.27
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs371987081; hg19: chr15-44630498;