NM_138423.4:c.450C>T

Variant names:

• chr15-44328752-C-T
• rs1047121563
• NM_138423.4:c.450C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_138423.4(GOLM2):​c.450C>T​(p.Asn150Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,074 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: GOLM2 NM_138423.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=0.303 with no splicing effect.

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.450C>T	p.Asn150Asn	synonymous	Exon 3 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.450C>T	p.Asn150Asn	synonymous	Exon 3 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.761C>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.450C>T	p.Asn150Asn	synonymous	Exon 3 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.450C>T	p.Asn150Asn	synonymous	Exon 3 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000557945.5	TSL:1	n.450C>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000453720.1	Q6P4E1-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459074 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725792

African (AFR) AF: 0.00 AC: 0 AN: 33362

American (AMR) AF: 0.00 AC: 0 AN: 44100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111034

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1047121563; hg19: chr15-44620950;